Introduction – In France, significant social inequalities in health persist, and employment is a social determinant that has a particular impact on mental health. To identify the populations that should be targeted for prevention efforts, it is necessary to better understand the differences in the prevalence of major depressive episodes (MDEs) between employed and unemployed individuals and to identify the social determinants at play.Method – Our study population consists of 14,471 working-age adults aged 18 to 64 residing in mainland France who were surveyed by telephone. The data were drawn from the 2021 Santé publique France Health Barometer. The estimates were weighted to account for the probability of inclusion and the population structure.Results – Unemployment within the past year was more common among unemployed working-age adults than among those with jobs, among men (16.7% versus 10.0%, p<0.001) and women (27.2% versus 15.5%, p<0.001). EDC was more common among younger individuals (ages 18–24), particularly among unemployed young women (34.5%). After adjusting for sociodemographic and economic characteristics, health behaviors, and the perceived impact of the COVID-19 period on morale, employment status remained significantly associated with EDC among women (adjusted odds ratio, aOR = 1.4 – 95% confidence interval: [1.1–1.8]), unlike men. Furthermore, living in a single-parent household appeared to strengthen the link between unemployment and EDC among unemployed women.Conclusion – Although the direct and indirect mechanisms underlying the link between unemployment and EDC remain to be better identified, targeted prevention efforts must focus on the unemployed working-age population, particularly younger women and those in single-parent families.