As distinct from mentally-active sedentary behaviors (e.g. reading), passive sedentary behaviors (e.g. TV-viewing) have been linked to a higher risk of depression, but the underlying mechanisms are unclear. We examined the potential mediating role of sleep problems in prospective relationships of passive sedentary behaviors with major depressive disorder (MDD).In 1997, 43 863 adults were surveyed and responses linked to clinician diagnoses of MDD until 2010. The questionnaire included items on sedentary behavior and sleep problems (Karolinska Sleep Questionnaire). Cox proportional hazard models and the 'counterfactual approach' were used to identify potential mediating effects of sleep problems in the association of passive sedentary behavior and MDD.Of the total sample, 3,065 (7.6%) were excluded for having indications of depression at baseline. Of 33,116 participants with complete data (mean age = 51.3 years, SD = 15.7, 64% female); 472 (1.4%) incident cases of MDD were identified during the 13-year follow-up. In Cox regression analyses, higher durations of passive sedentary behavior (≥3 h/day versus <3 h/day) were associated with greater hazards of developing MDD (HR = 1.27; 95% CI = 1.01, 1.58). This relationship remained after adjusting for confounders (HR = 1.29; 95% CI = 1.03, 1.63). Adding sleep problems into the analysis significantly attenuated these relationships (HR = 1.25; 95% CI = 0.99, 1.57). The excess MDD relative risk of passive sedentary behaviors due to sleep problems was statistically significant.Measures of sedentary behavior, physical activity and sleep were self-reported.Sleep problems appear to mediate detrimental associations of passive sedentary behavior with depression. Findings require further confirmation using objective measures.