Association of vitamin D with sepsis incidence and mortality: a large population-based prospective cohort study

Background: The role of vitamin D on the risk and clinical outcomes of sepsis remains incompletely elucidated. Objectives: This study aims to investigate the association between serum 25-hydroxyvitamin D [25(OH)D] concentrations and the risk of incident sepsis, and to evaluate its relationship with 28-day, 60-day, and 1-year mortality. Methods: In this prospective cohort study, we analyzed data from the UK Biobank. The association between serum 25(OH)D concentrations and sepsis incidence was evaluated using Cox proportional hazards models, Kaplan–Meier survival curves, and restricted cubic spline analyses. Results: Over a mean follow-up of 14 years, 15,452 incident sepsis cases were documented. A negative and nonlinear association was observed between serum 25(OH)D levels and sepsis risk. Compared with participants whose 25(OH)D levels were > 20 ng/mL, those with levels < 10 ng/mL exhibited an adjusted hazard ratio (HR) of 1.28 (1.22–1.34) for sepsis. This association was stronger among women and participants with a BMI < 25 kg/m2. Furthermore, participants with 25(OH)D < 10 ng/mL had significantly higher mortality than those with 25(OH)D > 20 ng/mL, with adjusted HRs of 1.14 (1.02–1.27) for 28-day mortality, 1.11 (1.01–1.23) for 60-day mortality, and 1.10 (1.02–1.19) for 1-year mortality. Conclusion: Lower serum 25(OH)D concentrations were associated with an increased incidence of sepsis and higher mortality. Supplementary Information: The online version contains supplementary material available at 10.1186/s13054-026-05977-z.