AbstractPurpose This study investigated the effects of psychosocial working conditions on mental health-related long-term sickness absence and whether distress, work satisfaction, burnout, engagement, and work ability mediated the associations between psychosocial working conditions and mental health-related long-term sickness absence. Methods This cohort study included 53,833 non-sick listed workers who participated in occupational health surveys between 2010 and 2013. The effects of the individual psychosocial working conditions on mental long-term sickness absence were analyzed using univariable and multivariable logistic regression analyses. Mediation analyses were performed to examine the mediating role of distress, burnout, work satisfaction, engagement, and work ability between psychosocial working conditions and mental long-term sickness absence. The mediation analyses were performed using structural equation modeling. Results Role clarity, cognitive demands, emotional demands, work variety, learning opportunities, and co-worker support were related to mental health-related long-term sickness absence after adjustment for other working conditions. The relationship between emotional demands and mental health-related long-term sickness absence was the strongest, OR 1.304 (p < 0.001, 95% CI 1.135 to 1.498). The relation between psychosocial working conditions and mental health-related long-term sickness absence was mediated by distress, burnout, work satisfaction, engagement, and work ability. Distress was the most important mediator between psychosocial working conditions and mental health-related long-term sickness absence. Conclusions Psychosocial working conditions are related to mental health-related long-term sickness absence. After correction for other working conditions, the association between emotional demands and mental health-related long-term sickness absence was the strongest. Psychosocial working conditions are indirectly related to mental health-related long-term sickness absence through mediation by distress, work satisfaction, and work ability.