Background: Outpatient physicians in private practice, as inpatient physicians, are on the frontline of the COVID-19 pandemic. Mental-health consequences of the pandemic on hospital staff have been published, but the psychological distress among outpatient physicians in private practice due to COVID-19 has never been specifically assessed. Methods: A French national online cross-sectional survey assessed declared psychological distress among outpatient physicians in private practice linked to COVID-19, sociodemographic and work conditions, mental health (Copenhagen Burn-out Inventory, Hospital Anxiety and Depression Scale, and the Insomnia severity Index), consequences on alcohol, tobacco, and illegal substance misuse, and sick leave during the 2nd COVID-19 wave. Findings: Among the 1,992 physicians who answered the survey, 1,529 (76.8%) declared psychological distress linked to COVID-19. Outpatient physicians who declared psychological distress linked to COVID-19 had higher rates of insomnia (OR = 1.4; CI95 [1.1-1.7], p = 0.003), burnout (OR = 2.7; CI95 [2.1; 3.2], p < 0.001), anxiety and depressive symptoms (OR = 2.4; CI95 [1.9-3.0], p < 0.001 and OR = 1.7; CI95 [1.3-2.3], p < 0.001) as compared to physicians who did not. They also had higher psychotropic drug use in the last twelve months, or increased alcohol or tobacco consumption due to work-related stress and were more frequently general practitioners. Interpretation: The feeling of being in psychological distress due to COVID-19 is highly frequent among outpatient physicians in private practice and is associated with mental health impairment. There is a need to assess specific interventions dedicated to outpatient physicians working in private practice.