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Objective Estimate the incidence of herpes simplex virus (HSV) infections in infants under 90 days in the UK and Ireland and describe clinical presentation and outcomes.Design Prospective population-based national surveillance study of infants <90 days with HSV infection, using British Paediatric Surveillance Unit (BPSU) methodology (August 2019–February 2022).Results 117 infants with confirmed HSV infection were identified (6.0 cases/100 000 live births (95% CI 4.9, 7.2)). One-third (34.5%) of infants were premature (<37 weeks) and the majority (81.4%) were born to women without a known/disclosed history of genital herpes. Neonatal HSV was classified as disseminated (32.5%), central nervous system (CNS) (35%) or skin, eye, mouth (SEM) (32.5%) disease. Median age at symptom onset was 8 days (IQR 5–13) in all infants (D8 SEM, D14 CNS, D6 disseminated). 56.7% of infants commenced aciclovir >24 hours after symptom onset. Infants with disseminated infections presented with non-specific signs of sepsis: 65.8% were afebrile and 73.7% had no SEM lesions. Median C reactive protein at presentation was 4 mg/L (IQR 1–14). Overall mortality was 23.9%, rising to 65.8% among infants with disseminated disease. Of the 41 infants with follow-up data at 24 months, 29.3% had neurodevelopmental impairment (11.8% SEM, 45% CNS, 25% disseminated).Conclusions Infants with neonatal HSV can present without fever, SEM lesions or elevated infection markers; treatment delay is subsequently common. Outcomes remain poor with high case-fatality rates and long-term morbidity. Clinicians should have a low threshold for empirically testing for and treating herpes in unwell neonates.