ObjectiveNeonatal infection with wildtype SARS-CoV-2 is rare and good outcomes predominate. We investigated neonatal outcomes using national population-level data to describe the impact of different SARS-CoV-2 variants.DesignProspective population-based cohort study.SettingNeonatal, paediatric and paediatric intensive care inpatient care settings in the UK.PatientsNeonates (first 28 days after birth) with confirmed SARS-CoV-2 infection who received inpatient care, March 2020 to April 2022. Neonates were identified through active national surveillance with linkage to national SARS-CoV-2 testing data, routinely recorded neonatal data, paediatric intensive care data and obstetric and perinatal mortality surveillance data.OutcomesPresenting signs, clinical course, severe disease requiring respiratory support are presented by the dominant SARS-CoV-2 variant in circulation at the time.Results344 neonates with SARS-CoV-2 infection received inpatient care; breakdown by dominant variant: 146 wildtype, 123 alpha, 57 delta and 18 omicron. Overall, 44.7% (153/342) neonates required respiratory support; short-term outcomes were good with 93.6% (322/344) of neonates discharged home. Eleven neonates died: seven unrelated to SARS-CoV-2 infection, four were attributed to neonatal SARS-CoV-2 infection (case fatality 4/344, 1.2% 95% CI 0.3% to 3.0%) of which three were born preterm due to maternal COVID-19. More neonates were born very preterm (23/54) and required invasive ventilation (27/57) when delta variant was predominant, and all four SARS-CoV-2-related deaths occurred in this period.ConclusionsInpatient care for neonates with SARS-CoV-2 was uncommon. Although rare, severe neonatal illness was more common during the delta variant period, potentially reflecting more severe maternal disease and associated preterm birth.Trial registration numberISRCTN60033461.