AbstractPeople with severe mental illness (SMI; including schizophrenia/psychosis, bipolar disorder (BD), major depressive disorder (MDD)) experience large disparities in physical health. Emerging evidence suggests this group experiences higher risks of infection and death from COVID-19, although the full extent of these disparities are not yet established. We investigated COVID-19 related infection, hospitalisation and mortality among people with SMI in the UK Biobank (UKB) cohort study. Overall, 447,296 participants from UKB (schizophrenia/psychosis = 1925, BD = 1483 and MDD = 41,448, non-SMI = 402,440) were linked with healthcare and death records. Multivariable logistic regression analysis was used to examine differences in COVID-19 outcomes by diagnosis, controlling for sociodemographic factors and comorbidities. In unadjusted analyses, higher odds of COVID-19 mortality were seen among people with schizophrenia/psychosis (odds ratio [OR] 4.84, 95% confidence interval [CI] 3.00–7.34), BD (OR 3.76, 95% CI 2.00–6.35), and MDD (OR 1.99, 95% CI 1.69–2.33) compared to people with no SMI. Higher odds of infection and hospitalisation were also seen across all SMI groups, particularly among people with schizophrenia/psychosis (OR 1.61, 95% CI 1.32–1.96; OR 3.47, 95% CI 2.47–4.72) and BD (OR 1.48, 95% CI 1.16–1.85; OR 3.31, 95% CI 2.22–4.73). In fully adjusted models, mortality and hospitalisation odds remained significantly higher among all SMI groups, though infection odds remained significantly higher only for MDD. People with schizophrenia/psychosis, BD and MDD have higher risks of COVID-19 infection, hospitalisation and mortality. Only a proportion of these disparities were accounted for by pre-existing demographic characteristics or comorbidities. Vaccination and preventive measures should be prioritised in these particularly vulnerable groups.