Objectives: To assess trends in overall health (mental and physical) and psychosocial factors in a population of workers (both healthcare and non-healthcare) in a French teaching hospital during the first year of the SARS-CoV-2 pandemic in France. Methods: A validated version of the SATIN questionnaire with adapted scoring was used to collect data on health and impacts of work stressors. This questionnaire was sent to all workers at the hospital in T1 (July–August 2020) and T2 (July–August 2021) and self-administered online. Results: A total of 1313 participants who completed the questionnaire at T1 and 826 at T2 were included. Overall, 568 workers completed the questionnaire at T1 and T2. We found a deterioration in overall health and especially stress and mental health in hospital workers and healthcare workers (HCWs), with a negative impact of the workload and work environment. Conclusions: The SARS-CoV-2 pandemic impacted negatively the mental health, work stressors, and psychosocial perceptions of both HCW and non-HCW in a French hospital. The study confirms that hospital workers are an important target.