OBJECTIVES: To investigate how lifestyle factors interact to affect the risk of contracting or dying of infection. STUDY DESIGN: Cohort study. METHODS: The UK Biobank is a large population-based cohort study that collected lifestyle factors and subsequently followed participants through healthcare records. The associations between physical activity, smoking and alcohol consumption and the risk of contracting or dying of infection was investigated. Lifestyle factors were analysed separately and in combination. RESULTS: Of 353,834 individuals, 47,075 suffered at least one infection and 4594 died of infection. Walking, moderate and vigorous physical activity demonstrated threshold patterns, where the greatest risk difference was between inactive individuals and individuals performing any activity. Smoking exhibited dose-response patterns, where more smoking was associated with higher risks. Alcohol demonstrated a J-shaped association, where both low and high consumption were associated with higher risk of contracting and dying of infection. Presence of adverse lifestyle factors in combination was associated with additively higher risk of contracting and dying of infection. CONCLUSIONS: Physical inactivity, smoking and alcohol consumption are associated with the risk of both contracting and dying of infection, with multiple factors having an additive effect. We suggest that infection be viewed as a lifestyle condition potentially amenable to preventative public health interventions.