Studies suggest a role for cardiovascular fitness in the prevention of affective disorders. To determine whether cardiovascular fitness at age 18 is associated with future risk of serious affective illness. Population-based Swedish cohort study of male conscripts (n = 1 117 292) born in 1950-1987 with no history of mental illness who were followed for 3-40 years. Data on cardiovascular fitness at conscription were linked with national hospital registers to calculate future risk of depression (requiring in-patient care) and bipolar disorder. In fully adjusted models low cardiovascular fitness was associated with increased risk for serious depression (hazard ratios (HR) = 1.96, 95%, CI 1.71-2.23). No such association could be shown for bipolar disorder (HR = 1.11, 95% CI 0.84-1.47). Lower cardiovascular fitness at age 18 was associated with increased risk of serious depression in adulthood. These results strengthen the theory of a cardiovascular contribution to the aetiology of depression.