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There is evidence to suggest a beneficial effect of physical activity on several mental disorders.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.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.Our findings suggest a joint association of leisure-time physical activity and sedentary behavior on the incidence of mental disorders.