Aims: This study examined the prospective association between male-female ratio in occupations and levels of effort-reward imbalance, burnout and sickness absence. Specifically, we examined whether levels of effort-reward imbalance, burnout and sickness absence differed by strata of occupational gender composition, and whether effort-reward imbalance explained these differences. Methods: Data from two waves of the Swedish Longitudinal Occupational Survey of Health (SLOSH) was used, forming a sample of 9051 participants. Chi-square test and one-way ANOVA were used to estimate differences in variables between strata of occupational gender composition, and multiple logistic regression analyses were performed to analyse if effort-reward imbalance explained differences in outcomes between five strata of occupational gender composition. The analyses were stratified by gender and level of education. Results: Levels of effort-reward imbalance, burnout and sickness absence varied by strata of occupational gender composition. Effort-reward imbalance was the most consistent predictor, while few significant associations were found between occupational gender composition and the outcomes. Effort-reward imbalance mediated some, but not all of the significant associations between occupational gender composition and the outcomes. Conclusions: There was no strong support for an association between occupational male-female ratio and burnout or sickness absence. Effort-reward imbalance was prospectively associated with all outcomes.