The authors report a case of aseptic meningitis associated with cephalosporins in an infant. A 1-year-old boy with trisomy 21 received several antimicrobials including cefotaxime and ceftriaxone for bacterial meningitis caused by Haemophilus influenzae b. High fever continued for more than a month, and discontinuation of cefotaxime broke the fever and improved the findings of cerebrospinal fluid. Because third-generation cephalosporins are the first choice against bacterial meningitis for infants, recognition and diagnosis of this rare occurrence of drug-induced aseptic meningitis is important. It is treatable by withdrawal of the drug, and recurrence can be prevented.