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Background: The adoption of healthy self-care practices has proven necessary for professional life, as they often serve as a shield against stressors in the workplace. The COVID-19 pandemic created a high strain on general practitioners (GPs), contributing to increased workload, burnout, and anxiety. The present study aimed to identify self-care practices adopted by GPs amid the COVID-19 pandemic; and to explore the relationships between self-care practices and risk of distress., Methods: The current study utilized an online questionnaire arriving from the PRICOV-19 study, which was distributed among GP practices across 38 countries. The main focus was on the open-text responses where participants disclosed self-care practices employed to maintain mental health during COVID-19. The Six Domains of Self-Care theoretical framework was applied to investigate GP self-care practices across 6 domains including Physical, Professional, Relational, Emotional, Psychological, and Spiritual. The Mayo Clinic Well-Being Index (eWBI) was applied to assess mental well-being and risk of distress among GPs. The analysis was carried out using SPSS Statistics software., Results: In total, 2,949 GPs provided open-text responses on maintaining their mental health. 65.5% of GPs had an eWBI score of ≥ 2 and were considered at risk of distress. The majority of the participants prioritised physical (61.7%), followed by relational (38.0%) and psychological (34.6%) self-care practices to maintain their mental health during the pandemic. GPs who applied relational, physical, and professional self-care were significantly less likely to experience depression, stress, and emotional exhaustion, in comparison with the ones who did not apply these practices. GPs who practiced professional self-care practices had the lowest distress risk (eWBI = 1.99). Overall, 5% of GPs disclosed not applying any practices to maintain their mental health during the pandemic and were the most prone to mental health distress., Conclusions: GPs have navigated the pandemic uniquely, and despite applying self-care practices they faced some level of impact, hence self-care interventions for healthcare professionals should be regarded as essential rather than optional. A long-term investment in strategies focused on improving GPs' self-care is necessary to increase resilience among GPs and ensure their optimal well-being levels are achieved., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki and was approved by the Research Ethics Committee of Ghent University Hospital (project number BC-07617). Additional research ethical approval was obtained in participating countries if required in that country or by the participating institution’s policies. The responses were anonymous; however, all respondents provided informed consent at the start of the questionnaire. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)