BACKGROUND: The problem of severe mental distress (SMD) in sub-Saharan Africa is difficult to investigate given that a substantial proportion of patients with SMD never access formal health care.This study set out to investigate SMD and it's associated factors in a rural population-based cohort in south-west Uganda. METHODS: 6,663 respondents aged 13 years and above in a general population cohort in southwestern Uganda were screened for probable SMD and possible associated factors. RESULTS: 0.9% screened positive for probable SMD. The factors significantly associated with SMD included older age, male sex, low socio-economic status, being a current smoker, having multiple or no sexual partners in the past year, reported epilepsy and consulting a traditional healer. CONCLUSION: SMD in this study was associated with both socio-demographic and behavioural factors. The association between SMD and high risk sexual behaviour calls for the integration of HIV prevention in mental health care programmes in high HIV prevalence settings.