Background: Health care workers (HCWs) are among the most vulnerable groups to experience burnout during the coronavirus (COVID-19) pandemic. Understanding the risk and protective factors of burnout is crucial in guiding the development of interventions; however, the understanding of burnout determinants in the Canadian HCW population remains limited.Objective: Identify risk and protective factors associated with burnout in Canadian HCWs during the COVID-19 pandemic and evaluate organizational factors as moderators in the relationship between COVID-19 contact and burnout.Methods: Data were drawn from an online longitudinal survey of Canadian HCWs collected between 26 June 2020 and 31 December 2020. Participants completed questions pertaining to their well-being, burnout, workplace support and concerns relating to the COVID-19 pandemic. Baseline data from 1029 HCWs were included in the analysis. Independent samples t-tests and multiple linear regression were used to evaluate factors associated with burnout scores.Results: HCWs in contact with COVID-19 patients showed significantly higher likelihood of probable burnout than HCWs not directly providing care to COVID-19 patients. Fewer years of work experience was associated with a higher likelihood of probable burnout, whereas stronger workplace support, organizational leadership, supervisory leadership, and a favourable ethical climate were associated with a decreased likelihood of probable burnout. Workplace support, organizational leadership, supervisory leadership, and ethical climate did not moderate the associations between contact with COVID-19 patients and burnout.Conclusions: Our findings suggest that HCWs who worked directly with COVID-19 patients, had fewer years of work experience, and perceived poor workplace support, organizational leadership, supervisory leadership and ethical climate were at higher risk of burnout. Ensuring reasonable work hours, adequate support from management, and fostering an ethical work environment are potential organizational-level strategies to maintain HCWs' well-being.