Background During the COVID-19 pandemic, many physicians experienced burnout, underscoring the need to identify factors associated with this condition to develop effective prevention and treatment strategies. Objective To examine the relationship between physician burnout and individual factors, medical errors, medical leave and the work environment. Design A cross-sectional online survey conducted from November 2020 to December 2020. Participants Physicians registered with the Medical College of Chile. Setting Registered physicians working in Chile across primary, secondary and tertiary levels of healthcare. Primary outcomes Burnout was assessed using the Maslach Burnout Inventory for Human Services. Secondary outcomes Self-reported medical errors, medical leave and turnover. Independent variables Sociodemographic characteristics, personality factors, psychological well-being, mindfulness factors, self-compassion and work environment factors. Descriptive statistics, linear and logistic regressions and regression analyses with cross-validation using least absolute shrinkage and selection operator (LASSO) tests were applied. Results Of the 23 481 registered physicians, 795 (3.4%) completed the survey. The sample included 64.1% women, with a mean age of 37.7 years (SD=11.3). The prevalence of burnout syndrome was 20.4% based on strict criteria and 68.9% based on lax criteria. Burnout scores predicted days of medical leave (ss=0.086, p<0.01), turnover (ss=0.012, p<0.05) and perceived medical errors (ss=0.009, p<0.001). In contrast, burnout was inversely correlated with age (ss=-0.125, p<0.001), agreeableness as a personality trait (ss=-0.107, p<0.001), psychological well-being (ss=-0.248, p<0.001) and the mindfulness factor awareness (ss=-0.145, p<0.001). In the work environment, time pressure (ss=0.167, p<0.001) was positively associated with burnout among others. Conclusion Younger physicians may be prioritised for individual-level interventions, while addressing time pressure at the organisational level could help prevent burnout. However, longitudinal studies are needed to clarify the directionality of relationships with psychological factors.