Various studies indicate that workload metrics can be used to assess inequities in the division of labor according to gender and in the mental health of health care professionals. In most studies, the workload is portrayed in a way that does not integrate the different fields of work, that is, work in health services and unpaid domestic work. The objective was to determine the effects of the workload domains of health work and unpaid domestic work according to the gender division of health professionals working in primary health care (PHC), and to analyze the workload as an inducer of anxiety disorders and episodes of depression. This cross-sectional study consisted of 342 health care professionals recruited for interview at primary health care units in the extreme south of Rio Grande do Sul, Brazil. Sociodemographic and occupational variables, workload in PHC and unpaid domestic work, and dichotomies of anxiety disorders and episodes of depression were considered. Poisson and multivariate linear regression models were used for data analysis. Cohen’s standardized effect size was used to assess the magnitude of the difference between women and men in terms of workload. The female professionals presented higher scores in terms of PHC work and unpaid domestic work and higher proportions of episodes of depression and anxiety disorders compared to males. The male professionals showed that anxiety disorders presented a medium standardized effect size on domestic workload and the level of frustration with family involvement was higher in those with episodes of depression. The results illustrate that the workload metric is an important indicator of female vulnerability to working conditions in PHC and in the family environment.