Objective To report a case of herpes simplex virus central nervous system infection in a neonate and to review literatures about this disease, and to improve clinical understanding of this rare disease and reduce misdiagnosis and missed diagnosis. Methods The clinical manifestation,diagnosis and treatment of the patient with herpes simplex virus central nervous system infection were analyzed.The epidemiology,clinical manifestation and key points of diagnosis were summarized from literature review. Results Literature review showed that: neonatal herpes simplex virus central nervous system infection is very rare. The mortality rate is high, and most of the survivors have adverse neurological outcomes. This case is a fourteen days newborn who was admitted to the hospital due to fever for unknown reasons. He was given acyclovir antiviral therapy immediately after admission and achieved good results. Follow-up of 3 months showed no neurological abnormalities. It suggested that early and effective antiviral therapy is a key factor affecting the prognosis. Conclusion Neonatal herpes simplex virus central nervous system infection has no specific clinical manifestations, and this disease is rare. Early, full-course of antiviral therapy can greatly improve the prognosis of children. For newborns with unexplained fever (especially those obtained in the community), early empirical antiviral treatment with acyclovir is more beneficial than harmful.