Abstract Background The English NHS Health Check is a unique national risk assessment, awareness and management programme for preventing cardiovascular disease (CVD), diabetes and chronic kidney disease (CKD). We aimed to assess their uptake and association with new diagnoses (CVD, hypertension, type-2 diabetes and CKD) in patients with severe mental illness (SMI) compared to patients without this condition and for patients on long-term antidepressant treatment (LTAD) (≥6 prescriptions vs < 6). Methods Cohort study (2013-2017) using the QResearch database. 1,319 general practices across England contributed of over nine million patients aged 40-74 years. 3,492,186 patients were eligible for NHS Health Checks of which 590,218 attended. Outcomes: hazard ratios (HR) with 95% confidence intervals (CI) for uptake of NHS Health Checks and for new diagnoses within 1 year in attendees. Models were adjusted for sex, age, ethnicity, deprivation and region. Results 65,490 people with SMI and 46,437 people on LTAD (20% of the total eligible with SMI/LTAD, respectively) attended an NHS Health Check. People with SMI or on LTAD were more likely to attend compared to people without those conditions, adjusted HRs 1.05 (95% CI 1.02-1.08) and 1.10 (95% CI 1.08-1.13), respectively. Among attendees, people with SMI and on LTAD were 23% and 55% more likely to be diagnosed with CKD (95% CI 1.12-1.34 and 1.42-1.70, respectively) than people without these conditions. Attendees on LTAD were 66% more likely to have a major CVD event within 1 year than those without LTAD (95% CI 1.41-1.94) or a new diagnosis of hypertension and type 2 diabetes, HRs 1.12 (95% CI 1.05-1.20) and 1.45 (95% CI 1.31-1.60), respectively. Conclusions People with SMI or on LTAD were more likely to attend NHS Health Checks than people without these conditions. Higher rates of CKD in patients with SMI/LTAD and CVD, hypertension and type 2 diabetes in the latter might indicate increased risks and unmet need in these patient groups Key messages People with SMI/LTAD were more likely to attend NHS Health Checks. People on LTAD were more likely to be diagnosed with CVD, CKD, hypertension and type-2 diabetes than people without these conditions. SMI attendees were more likely to be diagnosed with CKD.