Objectives Healthcare workers (HCWs) are the front lines during the COVID-19 pandemic. They are more exposed to COVID-19 than other professions. Studies from other countries have shown that the mental health and health-related quality of life (HRQoL) of HCWs were affected during this pandemic. However, studies on mental health in Indonesia remain scarce and no study has evaluated the HRQoL among HCWs. Thus, this study was designed to explore the mental health status and HRQoL among HCWs in Indonesia. Design This was a cross-sectional study. Setting This was an open online survey in Indonesia conducted from December 2020 to February 2021. Participants This study involved HCWs who worked during the COVID-19 pandemic. Of the 502 respondents who accessed the online questionnaire, 392 were included in the analysis. Outcomes Mental health status was measured using the 21-item Depression, Anxiety and Stress Scale and HRQoL was measured using the second version of the 12-item Short-Form Health Survey (SF12v2). Results The prevalence of depression, anxiety and stress among HCWs was 29.4%, 44.9% and 31.8%, respectively. Using the SF12v2 questionnaire, 354 (90.3%) HCWs were found to have impaired physical component and 156 (39.8%) HCWs have impaired mental component. Conclusion The prevalence of mental health problems among HCWs was high in Indonesia. HRQoL, particularly the physical component, was affected in most HCWs. Thus, policymakers should give more attention to the mental health and HRQoL of HCWs during the COVID-19 pandemic.