PURPOSE: There is evidence to suggest a beneficial effect of physical activity on several mental disorders. METHODS: The study aim was to assess the association between low physical activity during leisure time (or sedentary lifestyles) and the incidence of mental disorders in 10,381 participants, from a Spanish dynamic prospective cohort of university graduates followed up for 6 yr (the SUN study). The baseline assessment included a validated questionnaire on physical activity during leisure-time and sedentary activities. A subject was classified as an incident case of mental disorder if he or she reported a physician diagnosis of depression, anxiety or stress, and/or the use of antidepressant medication or tranquilizers in at least one of the follow-up questionnaires. RESULTS: The odds ratios (OR) and 95% confidence intervals (CI) of a mental disorder for successive levels of leisure-time physical activity were 1 (reference), 1.00 (0.81, 1.23), 0.99 (0.81, 1.21), 0.72 (0.58, 0.89), and 0.81 (0.65, 1.00) (P for trend: < 0.01). The OR for subjects who spent more than 42 h.wk(-1) watching television and/or using the computer was 1.31 (95% CI = 1.01, 1.68) as compared with those spending less than 10.5 h.wk(-1). CONCLUSION: Our findings suggest a joint association of leisure-time physical activity and sedentary behavior on the incidence of mental disorders.