Coronavirus Disease 2019 (COVID-19) has become a global health threat and has placed an extraordinary demand for healthcare workers around the world. In this study, we aim to examine the prevalence of burnout, its associating factors, and experience among Malaysian healthcare workers through an embedded mixed-method study design. We found that more than half of Malaysian health care workers in this sample experienced burnout. Direct involvement in COVID-19 screening or treatment, having a medical condition, and less psychological support in the workplace emerged to be the significant factors for personal-, work- and patient-related burnout. Participants described workload, uncertainties from the pandemic, challenged work-family balance and stretched workplace relationships as the sources of burnout. Exhaustion appeared to be the major symptom and many participants utilized problem-focused coping to deal with the adversities experienced during the pandemic. Participants reported physical, occupational, psychological, and social-related negative impacts emanating from burnout. As the pandemic trajectory is yet unknown, the findings provide early insight and guidance for possible interventions.