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Background People with severe mental illness (SMI) have a higher risk of infection-related hospitalisations than the general population, yet the reasons why remain poorly understood.Objective We aimed to identify factors associated with infection-related hospitalisations and to explore how these factors cluster together within the patient population.Methods We conducted a retrospective cohort study using linked electronic health records from a large secondary mental health service in South London. Individuals with an SMI diagnosis between 1 January 2007 and 31 December 2019 were included. Cox regression models examined associations between a wide range of sociodemographic, health-related, clinical and treatment and service-use factors and time to first infection-related hospitalisation. Significant factors were then used in a hierarchical cluster analysis to identify distinct patterns.Findings In 19 995 individuals with SMI, several factors associated with infection-related hospitalisations emerged, with the strongest being number of general hospital admissions for ambulatory care sensitive conditions (HR=2.31, 95% CI 2.08 to 2.56), clozapine prescribing (HR=1.67, 95% CI 1.45 to 1.92) and severe problems with physical illness/disability (HR=1.36, 95% CI 1.31 to 1.42). Two distinct patterns emerged: one characterised by older age, dementia and poor physical health; the other by younger age with complex psychiatric needs and use of alcohol and other substances.Conclusions1 This study identified several factors associated with infection-related hospitalisations and highlighted how these factors tend to group together among people with SMI.Clinical implications These findings indicate potential areas where tailored prevention and monitoring strategies may be warranted to help reduce the likelihood of infection-related hospitalisation in people with SMI alongside broader measures such as prioritisation for pneumococcal and influenza vaccination.