Background: The COVID-19 pandemic, by putting practices of general medicine under intense strain, has shed a harsh light on the weaknesses of our health care system. One of these weaknesses is the low level of general practitioner (GP) well-being. While recent literature has highlighted the huge toll the pandemic has had on GP's mental health, few studies have examined the relationship between the unexpected structural and organizational challenges caused by COVID-19 and GPs’ wellbeing. Objective: This study explores workplace-related stress factors on GP's wellbeing during the pandemic in Belgium, with an inter-regional comparison, and identifies the potential key organizational and structural levers that could help promote Belgian GPs wellbeing after the crisis. Study setting: Data from the PRICOV-19 study, a multi-country cross-sectional study under the coordination of Ghent University (Belgium), was used. Methods: Belgian general practitioners were recruited between December 2020 and August 2021 in the three Belgian regions. A pseudonymized survey was used for data collection using an online self-reported questionnaire. The Mayo Clinic Well-being Index was used to evaluate GP's well-being. Statistical analysis was performed using SPSS Statistics. Descriptive statistics and chi-squared tests were performed. Results: 479 Belgian GP practices completed the survey. 57% of Belgian GPs were considered at risk of distress during the pandemic. Those numbers varied between regions, with 72,9% in the Walloon Region, 54,5% in the Brussel-Capital Region, and 48,6% in the Flemish Region. The study shows the influence of some organizational and structural factors on GPs wellbeing. This influence varies between regions. Among these factors are the support received from the government, the ability to distribute the workload within the practice and between practices, the practice organization, the work experience, and time left for private life. Discussion: For GPs, social responsibility lies in meeting the health needs of ...