Purpose: To investigate if sick leave due to mental disorders increases the risk of morbidity measured by inpatient and specialized outpatient care, and mortality among women and men, independent of familial factors. Methods: An open cohort study of 4979 twin pairs discordant for sick leave due to mental disorders was conducted in 2005–2013. Twins were followed up in the cause of death and national patient registries until the end of study, emigration, death, and inpatient and specialized outpatient care. Conditional Cox proportional hazard regression, adjusting for the familial factors shared by the twins, was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). In case of non-proportional hazards, time-varying covariates were used. Results: Sick leave due to mental disorders increased the risk for inpatient care among men (HR: 1.90, CI 1.66–2.17) and women (HR: 1.39, CI 1.27–1.51). For men, the risk of outpatient care was higher the first 2 years (HR: 2.08, CI 1.87–2.31), after which it was attenuated (HR: 1.32, CI 1.02–1.70). For women, the HR was 1.57 (CI 1.47–1.68) for the whole study time. There was an increased risk of death among men (HR: 2.91, CI 1.70–4.99), but not among women (HR: 0.84, CI 0.53–1.35). Conclusions: Sick leave due to mental disorders was a risk factor for mortality for men only, and increased the risk of inpatient and specialized outpatient care among both women and men, but the risks were higher for men when stratifying for sex.