Objectives: Adopting the protection motivation theory and self-determination theory as frameworks, the present study examined whether the mental well-being of health care workers is determined by a combination of COVID-19-related factors (exposure and resources), organizational factors, and individual and attitudinal factors. Methods: The present study is based on Eurofound's Living, Working, and COVID-19 survey, and the fieldwork for this survey was performed via uncontrolled convenience sampling throughout June and July 2020 in the 27 European Union countries. This research utilized a subsample of 1824 health sector employees and 11,750 workers in the other service industries. Further, to meet the objectives of this study, different linear regression models are estimated. Results: Despite the close contact of health care workers with COVID-19, we found that the risk of contracting the coronavirus does not explain their poor or high well-being. However, the availability of personal protection equipment and mistrust in the national health system contribute to well-being, along with other organizational (eg, job insecurity) and individual-attitudinal factors (eg, health and life satisfaction). Conclusions: The present study offers various valuable insights for health institutes, organizations, practitioners, and employers to combat COVID-19 and identify the determinants of the mental well-being of health care professionals.