Background: Nursing homes were particularly affected by the COVID-19 pandemic. The purpose of this study was to evaluate qualitatively and quantitatively with the use of a self-reported questionnaire as a tool for screening for mental disorders in nursing home staff. Methods: A multicenter epidemiological study was conducted in 12 nursing homes in France with 1117 nursing home staff eligible. Socio-demographic, occupational, and medical data were collected by anonymous self-reported questionnaire using validated scales to assess anxiety/depressive symptoms (HAD scale) and post-traumatic stress disorder (PCL-5). A total of 12 semi-structured interviews were conducted to assess acceptance and expectations for the use of the questionnaire. Results: The participation rate was 34.5%. Data from 373 questionnaires were included in the analysis. The questionnaire was well accepted by the participants and met their wishes for prevention action. The sample was 82% female. More than half reported a feeling of powerlessness and lack of time or staffing. The prevalence of anxiety symptoms was 22%, depressive symptoms 10%, and post-traumatic stress 7%. Conclusion: This study underlines the interest in screening for mental disorders by self-reported questionnaire and deploying preventive actions in the workplace to reduce stress and facilitate the reconciliation of family and working life in this context of the pandemic.