ObjectiveTo investigate SARS-CoV-2 vaccine uptake and effectiveness in children and young people (CYP) with life-limiting neurodisability.DesignWe undertook a retrospective cohort study using national hospital data in England from 21 December 2020 to 2 September 2022 to describe SARS-CoV-2 vaccination uptake, and then examined COVID-19 hospitalisation, paediatric intensive care unit (PICU) admission and death following SARS-CoV-2 infection by vaccination status using Cox regression models.PatientsCYP aged 5–17 with life-limiting neurodisability.ResultsWe identified 38 067 CYP with life-limiting neurodisability; 13 311 (35.0%) received at least one SARS-CoV-2 vaccine, with uptake higher among older, white CYP, from less deprived neighbourhoods. Of 8134 CYP followed up after a positive SARS-CoV-2 test, 1547 (19%) were vaccinated. Within 28 days of infection, 309 (4.7%) unvaccinated CYP were hospitalised with COVID-19 compared with 75 (4.8%) vaccinated CYP. Of 46 (0.7%) unvaccinated CYP were admitted to PICU compared with 10 (0.6%) vaccinated CYP. Of 20 CYP died within 28 days of SARS-CoV-2 infection, of which 13 were unvaccinated. Overall, adjusted hazard of hospitalisation for COVID-19 or admission to PICU did not vary by vaccination status. When the Alpha-Delta SARS-CoV-2 variants were dominant, hazard of hospitalisation with COVID-19 was significantly lower among vaccinated CYP (HR 0.26 (0.09 to 0.74)), with no difference seen during Omicron (HR 1.16 (0.74 to 1.81)).ConclusionsSARS-CoV-2 vaccination was protective of COVID-19 hospitalisation among CYP with life-limiting neurodisability during Alpha-Delta, but not for other SARS-CoV-2 variants. Vaccine uptake was low and varied by ethnicity and deprivation.