Infected cephalohematoma is rarely complicated by sepsis. We report a case of an infected cephalohematoma caused by Escherichia coli sepsis in an otherwise healthy neonate. Skull X-ray revealed soft tissue swelling over parieto-temporal region but no osteolytic lesion. 99mTc bone scan showed scalp cellulitis. Blood culture and scalp wound culture identified E. coli. Treatment with surgical incision and drainage and administration of antibiotics resulted in prompt improvement. The relationship of scalp cellulitis, infected cephalohematoma, and sepsis are discussed.