Febrile seizures, which are convulsion in children, are caused by an abrupt increase in body temperature. They are sometimes recurrent, and the more seizures are triggered, the higher the risk of epilepsy and psychiatric disorders increase after growing up. Prevention of febrile seizure is considered to be one of the effective countermeasures in protecting the future health of children; however, pharmacological prevention in the developmental stage is not realistic from the health aspects of the offspring. Docosahexaenoic acid (DHA) is an important nutrient especially during pregnancy and childhood and is reported to suppress several types of epilepsy. The purpose of this study was to examine the effect of DHA intake during pregnancy and infancy on febrile seizures in mice. We used a heat chamber for febrile seizure induction in offspring at the age of from 10 to 11 days old. Intake of DHA during pregnancy and infancy significantly increased the amount of DHA in the brain of offspring. Although DHA had no effect on seizure severity, DHA significantly prolonged the seizure latency and increased body temperature at which the first seizure occurred, indicating that maternal DHA intake decreases febrile seizure sensitivity. Brain estrogen levels significantly increased by DHA intake and administration of an inhibitor for cytochrome P450 aromatase, which is a rate-limiting enzyme for estrogen synthesis, clearly decreased seizure latency and body temperature at which the first seizure occurred. Taken together, DHA could reduce susceptibility to febrile seizures owing to increases in brain estrogen contents. DHA intake during pregnancy and infancy is of significance in protecting infant from seizures as well as conserving health after growth.