Fevers are one of the most common side effects of vaccination. Often, fevers are associated with illness, and, therefore, it is understandable that parents have concerns when their child develops a fever after vaccination. However, fevers are a normal part of immune responses. So, a fever after vaccination offers evidence that the child’s immune system is responding to the vaccine, and as a result, building immunity against the virus or bacteria that the vaccine targets.

What is a fever?

A fever is a body temperature that is higher than normal. Most people have a normal body temperature around 98.6ᴼF (37ᴼC). But, baseline body temperatures vary between people, and they also vary throughout the day within individuals. 

Because fevers are associated with illness, many people think of them as a bad thing. But, fevers, even high fevers, are a normal and important part of the immune response. First, by turning up the temperature in the body, fevers make the body a less welcoming host for germs, thereby limiting their ability to reproduce in the body. Second, higher temperatures also serve to activate some of the signaling chemicals that guide immune responses.

Why do vaccines cause fevers?

Vaccines prepare the immune system to protect against viruses or bacteria that could make people sick. The way this happens is that they introduce components of the germs that are known to activate the immune response. However, vaccines will not cause a significant enough immune response that the person suffers untoward events, such as can occur during natural infections. With this said, in some cases the immune response is strong enough to cause detectable symptoms, like a mild fever.

Knowing that vaccines can cause a fever, sometimes parents wonder if a lack of fever means the vaccine is not working. However, not everyone who responds to a vaccine will develop a fever.

How high do fevers get after vaccination?

Sometimes a rapid rise in a child’s temperature, not the actual height of the temperature, will cause a fever-induced (febrile) seizure. While febrile seizures are scary, they do not result in permanent or long-lasting effects. One study suggested that less than 7% of febrile seizures in children younger than 6 years of age were caused by vaccinations. The researchers also found that febrile seizures following receipt of vaccines were not different from those caused by infections when it came to duration, likelihood of another seizure in the same 24-hour period, need for ICU admission, length of hospital stay, or requirement for anti-seizure medications. Any questions or concerns about fevers should be discussed with a healthcare provider, and an episode of a febrile seizure should be reported to the healthcare provider, so that it can be added to the child’s medical record.

When should I expect a fever to appear after vaccination?

Most fevers occur within a week of vaccination; however, because vaccines cause immunity in different ways, depending on how they are made, there is some variation regarding exactly when fevers following vaccination are most likely to occur. Additionally, because some vaccines require more than one dose to be effective, fevers may be more likely after later doses. The timing and frequency of fevers after many common vaccines are listed below.

Vaccines against individual pathogens

COVID-19

• Pfizer-BioNTech mRNA vaccine, 1-2 days after vaccination, lasting 1 day in 10-20 of 100 vaccine recipients when given as a booster dose. Fever occurs less frequently in an unvaccinated vaccine recipient.
• Moderna mRNA vaccine (adults), 1-2 days after vaccination, lasting 1 day in 10 of 100 adult vaccine recipients when given as a booster dose. Fever occurs less frequently in an unvaccinated vaccine recipient.
• Moderna mRNA vaccine (children), 1-2 days after vaccination, lasting 1 day in 20-30 of 100 children when given as a booster dose. Fever occurs less frequently in an unvaccinated vaccine recipient.
• Novavax COVID-19 vaccine, 1-3 days after vaccination, lasting 1-2 days in 1-17 of 100 vaccine recipients. Fever occurs less frequently in older age groups.

Haemophilus influenzae type b (Hib)

• ActHIB, 2 days after vaccination in about 2 of 100 vaccine recipients
• Hiberix, 4 days after vaccination in 14-19 of 100 vaccine recipients; fevers occur more frequently after the second and third doses
• PedvaxHIB, 6 to 48 hours after vaccination in 1-18 of 100 vaccine recipients

Hepatitis B

• Heplisav-B, 0 to 7 days after vaccination in 1-2 of 100 vaccine recipients
• Engerix B, 1 to 17 days after vaccination in 2 of 100 vaccine recipients
• Recombivax, in 1-10 of 100 vaccine recipients

Hepatitis A

• Havrix, 0 to 4 days after vaccination in 3 of 100 vaccine recipients
• Vaqta, 1 to 5 days after vaccination in 10 of 100 vaccine recipients

Human papillomavirus

• Gardasil 9, 0 to 5 days after vaccination in 6-7 of 100 vaccine recipients

Meningitis ACWY

• Menactra, 0 to 7 days after vaccination in 5-12 of 100 vaccine recipients; fevers occur more frequently in those younger than 2 years of age
• Menveo, 0 to 7 days after vaccination in 3-9 of 100 vaccine recipients; fevers occur more frequently after the third and fourth doses
• Menquadfi, 0 to 7 days after vaccination in 1-2 of 100 vaccine recipients

Meningitis B

• Trumenba, 0 to 7 days after vaccination in 2-6 of 100 vaccine recipients; fevers occur more frequently after the first dose
• Bexsero, 0 to 7 days after vaccination in 1-4 of 100 vaccine recipients; fevers occur more frequently after the second dose

Pneumococcal

• Prevnar 13 (conjugate version), 0 to 7 days after vaccination in 24-35 of 100 infant vaccine recipients; fewer than 10 of 100 older children who receive this vaccine will experience fever
• Pneumovax 23 (polysaccharide version), 1-2 of 100 vaccine recipients will experience fever

Rotavirus

• RotaTeq, 0 to 7 days after vaccination in 17-20 of 100 vaccine recipients
• Rotarix, 0 to 7 days after vaccination in 25-28 of 100 vaccine recipients

Varicella (chickenpox)

• Varivax, 0 to 42 days after vaccination in 10 of 100 vaccine recipients; most fevers occur 14 to 27 days after vaccination

Shingles (zoster)

• Shingrix, 0 to 7 days after vaccination in 28 of 100 vaccine recipients 50 to 59 years of age; in 24 of 100 vaccine recipients 60 to 69 years of age; in 14 of 100 vaccine recipients 70 years of age and older

Vaccines against multiple pathogens

Measles, mumps, and rubella

• MMR II, 0 to 14 days after vaccination in 2 of 100 vaccine recipients

DTaP

• Daptacel, 0 to 3 days after vaccination in 11-20 of 100 vaccine recipients
• Infanrix, 0 to 4 days after vaccination in 8-12 of 100 vaccine recipients; fevers occur more frequently after the second dose

DTaP combined with other components (combination vaccines)

• Plus polio - Quadracel, 0 to 7 days after vaccination in 6 of 100 vaccine recipients
• Plus polio – Kinrix, 0 to 4 days after vaccination in 1 of 100 vaccine recipients
• Plus polio and Hib - Pentacel, 0 to 3 days after vaccination in 6-16 of 100 vaccine recipients
• Plus polio and hepatitis B - Pediarix, 0 to 4 days after vaccination in 28-39 of 100 vaccine recipients
• Plus polio, Hib, and hepatitis B – Vaxelis™, 0 to 5 days after vaccination in 19 to 29 of 100 vaccine recipients (Prevnar 13 and RotaTeq were also administered at the same visit)

Tdap

• Boostrix, 0 to 15 days after vaccination in 19 of 100 vaccine recipients
• Adacel, 0 to 15 days after vaccination in 1-5 of 100 vaccine recipients; fevers occur more frequently in children than adults

Hepatitis A and hepatitis B

• Twinrix, 0 to 4 days after vaccination in 2-4 of 100 vaccine recipients

Measles, mumps, rubella, and varicella (chickenpox)

• ProQuad, 0 to 5 days after vaccination in 8-20 of 100 vaccine recipients; fevers occur most frequently after the first dose

What about medications for fever?

Should I give my child medication prior to a vaccine visit to prevent fever after vaccination?

No. Giving medication prior to a vaccine visit is not recommended because they may decrease the child’s immune response to the vaccine. Studies of patients who got fever-reducing medication prior to vaccination had lower antibody responses compared with patients that did not receive medicine, suggesting that their immune response to the vaccine was lower as a result of reducing the fever.

Should I give my child medication to treat a fever after vaccination or during illness?

In most cases a child does not need to be medicated for a fever unless they are extremely uncomfortable. The most important thing to do when a child has a fever is to make sure they stay hydrated by drinking plenty of fluids. If you are not sure whether the child should get medicine to address fever or other symptoms, talk to your child’s healthcare provider. 

What are the concerns with glutathione and vaccines?

Some people have raised concerns that acetaminophen (e.g., Tylenol) depletes glutathione and, therefore, should not be used before vaccination. Others have suggested that vaccines directly deplete glutathione, causing inflammation. However, these claims conflate some biological concepts and further, they remain unsupported by evidence. Let’s dig in a bit though.

Generally speaking, treating fever by giving acetaminophen before or after vaccination is not recommended, but the recommendation is not related to glutathione. Fever is a tool of our immune system that helps in two ways. First, some aspects of our immune system are more efficient at higher temperatures. Second, pathogens are not adapted to be as infectious at higher temperatures. When it comes to vaccines, some studies have demonstrated that while giving acetaminophen before vaccination reduces the likelihood of fever after vaccination, it also reduces the immune response to the vaccine, making the vaccine less effective. When it comes to treating fever after vaccination, the rule of thumb is usually that if the child has a fever that is high enough that they are uncomfortable, it is OK to give them acetaminophen, but if they are doing OK without the medication, it is better to let the fever do its job. If you are unsure, always talk to your child’s doctor to see what makes sense for your situation.

Now, back to glutathione. Glutathione is made of three amino acids (the building blocks of proteins). It is produced and recycled by the body. Glutathione is an antioxidant, which means that it protects the body from harmful substances called free radicals. Free radicals can cause inflammation; however, inflammation is a complex biological condition, so pointing to a specific chemical (e.g., glutathione) and suggesting that its levels alone determine inflammation is too simplistic. Three points are important: 

1. Acetaminophen and glutathione — Glutathione helps inactivate harmful molecules that are made when acetaminophen is processed. If a person ingests too much acetaminophen, such as by taking extra doses of a single acetaminophen-containing medication or by mixing multiple medications that each contain acetaminophen, the body’s store of glutathione can be insufficient to inactive the harmful molecules produced during acetaminophen processing. In some cases, this can lead to liver damage. Offering acetaminophen for a child who had a vaccine is not going to deplete an individual’s glutathione to a point of causing harm.
2. Vaccines and inflammation — Vaccines work by exposing the body to a weakened or inactivated version of a pathogen so that the immune system learns how to respond to that pathogen in the future. The immune system’s response can cause temporary inflammation near the injection site, which is why some people may have a sore arm after vaccination. Some research has suggested that this localized inflammation following vaccination may indicate a stronger immune response. Importantly, the temporary inflammation that can happen following vaccination is different from the chronic inflammation that can lead to diseases, such as cancer and diabetes.
3. A condition that results in lower levels of glutathione — Glucose 6 phosphate dehydrogenase (G6PD) is an enzyme involved in the biological pathway that creates glutathione in our bodies. Some people develop a condition known as G6PD deficiency in which their bodies don’t produce enough G6PD. People with G6PD can experience excess breakdown of red blood cells, resulting in anemia. They can also have symptoms like yellowing of the skin and shortness of breath. Because of the role of G6PD in producing glutathione, people with this condition often also have lower levels of glutathione. However, affected individuals are not more likely to have negative outcomes from vaccination, and, in fact, they are recommended to get vaccines to prevent infections that can trigger some of the other symptoms of this condition.

For these reasons, vaccines are unlikely to cause or trigger untoward health effects related to glutathione.