Abstract: OBJECTIVE To explore the causes of herpes simplex virus type 1 (HSV-1) encephalitis in neonates, observe the clinical manifestations, diagnosis, treatment and prognosis, raise the awareness of the diseases, improve the diagnosis and treatment levels, and reduce the missed diagnosis and misdiagnosis. METHODS The medical data were collected from 2 neonates with HSV-1 encephalitis who were treated in Women and Children's Hospital Affiliated to Ningbo University from Jan. 2021 to Jul. 2025 and were retrospectively analyzed. Relevant keywords were retrieved to search for Chinese and foreign literature released from Jan. 2015 to Oct. 2025. Totally 8 literatures that were eligible for inclusion criteria were reviewed. RESULTS The mothers of the 2 neonates were primipara and were tested negative for TORCH in the third trimester, but they were complicated with genital tract infections and gave birth through cesarean section. The neonates were hospitalized due to fever more than 1 week and resuscitation from asphyxia, respectively. The core clinical manifestations included fever, respiratory abnormalities and abnormal indicators of multiple organs. The conformed diagnosis was made based on the clinical laboratory test, etiological tests (metagenomic next-generation sequencing) and imaging findings. The neonates were given acyclovir for antiviral therapy (with the courses 6 months and 3 weeks, respectively), anti-infection therapy and symptomatic therapy, and no nervous system-related sequela were found after 1 and 3 years of follow-up. The literature review indicated that the initial symptoms of the neonates with HSV-1 encephalitis were diverse, the brain lesions were mainly located in the frontoparietal temporal lobes. Acyclovir was the main therapeutic drug, but the prognosis of most cases was poor. CONCLUSIONS The HSV-1 encephalitis is less common among the neonates, the routes of the infection may included the maternal inapparent infection and indirect transmission related to disturbance of genital tract flora. mNGS may facilitate the early diagnosis, the standardized and full dose of acyclovir as well as the enhancenment of immune function of host may improve the prognosis. It is necessary for the hospital to attach great importance to the serological identification, prevention and control of health care-associated infections.