Following the first lockdown implemented in France in response to the COVID-19 pandemic, Santé publique France conducted a survey between May and August 2020 among 27,000 current and former workers in the agricultural social security system and 20,000 current and former self-employed workers in the Coset cohorts. The aim was to document the pandemic’s impact on the professional activity of these populations and assess their health status upon exiting lockdown. Non-agricultural self-employed individuals experienced mostly complete interruptions in activity, particularly women, while agricultural employees experienced partial interruptions. For those who continued working, significant changes in working conditions were reported. The impacts of this period on health and behavior were significant, though with visible contrasts between genders and occupational subgroups. Certain occupational groups exhibited a higher prevalence of anxiety and depressive symptoms following the end of lockdown. The frequency of these disorders was associated with certain occupational factors related to unfavorable working conditions during the lockdown. These observations regarding professionals made vulnerable by management measures complement other studies on workers’ mental health in relation to the COVID-19 pandemic. They will provide prevention stakeholders and social partners with insights to address future crises and explore alternative ways of working.