An infected cephalhematoma is a rare condition in neonates. We report a case of an 18-day-old neonate who was diagnosed with an infected cephalhematoma caused by an extended spectrum beta-lactamase (ESBL)-producing Escherichia coli complicated with septicemia, meningitis, and skull osteomyelitis.b He was successfully treated with meropenem and surgical incision and drainage. ESBL-producing E. coli may cause infection of a cephalhematoma in neonates.