We report a case of Escherichia coli infection of a cephalohematoma in an infant delivered by vacuum extraction. After excluding potential complications, the patient was treated with intravenous ceftriaxone while hospitalized followed by oral cephalexin after discharge. Infection is a rare but serious complication of cephalohematomas in the newborn period. Escherichia coli is the most common pathogen responsible for infected cephalohematomas. Clinicians should be aware that infected cephalohematomas may be complicated by sepsis, meningitis, or osteomyelitis.