We reviewed the characteristics of infants <3 months of age with central nervous system herpes simplex virus infection at our institution. Twenty-six cases were identified. The age range was 4–73 days. Most infants presented with fever, seizure activity and skin lesions. The blood herpes simplex virus polymerase chain reaction was positive in 91% of patients tested. Suppressive oral acyclovir therapy was likely helpful in preventing disease recurrence.