Introduction: Health care workers (HCWs) are directly involved in processes linked with diagnosis, management, and assistance of coronavirus disease-19 (COVID-19) patients which could have direct implications on their physical and emotional health. Emotional aspects of working in an infectious pandemic situation is often neglected in favour of the more obvious physical ramifica-tions. This single point assessment study aimed to explore the factors related to stress, anxiety and depression among HCWs consequent to working in a pandemic. Material and Methods: This was a cross-sectional study involving healthcare workers who were working in COVID-19 inpatient ward, COVID-19 screening area, suspect ward, suspect intensive care unit (ICU) and COVID-19 ICU across four hospitals in India. A web-based survey questionnaire was designed to elicit responses to daily challenges faced by HCWs. The questionnaire was regressed using machine-learning algo-rithm (Cat Boost) against the standardized Depression, Anxiety and Stress Scale-21 (DASS 21) which was used to quantify emotional distress experienced by them. Results: A total of 156 participants were included in this study. As per DASS-21 scoring, severe stress was seen in ~17% of respondents. We could achieve an R2 of 0.28 using our machine-learning model. The major factors responsible for stress were decreased time available for personal needs, increasing age, being posted out of core area of expertise, setting of COVID-19 care, increasing duty hours, increasing duty days, marital status and being a resident physician. Conclusions: Factors elicited in this study that are associated with stress in HCWs need to be addressed to provide wholesome emotional support to HCWs bat-tling the pandemic. Targeted interventions may result in increased emotional resilience of the health-care system.