Context: Frontline healthcare workers are at risk of developing psychological distress during a pandemic. Yoga, a form of mind-body medicine can reduce body stress and increases well-being.Aims: To assess the effect of yoga on the stress and well-being of healthcare workers during the COVID-19 pandemic.Settings and design: This single-arm pre-post study was conducted among frontline health workers (support staff, paramedics, and medics) posted at a secondary care hospital in a North Indian district.Methods and materials: Basic demographic details, blood pressure, anthropometric variables like height, weight, and biochemical variables like glycosylated hemoglobin (Hb1Ac), fasting and post-prandial blood sugar, lipid profile, serum cortisol, and C-reactive protein were measured. Stress levels were assessed using the depression anxiety and stress scale (DASS)-21 while well-being was assessed using the World Health Organization (WHO)-5 well-being scale. Twelve weeks of supervised yoga session was provided for 1 hour per session, 3 times per week.Statistical analysis: The mean value was compared from baseline to post-intervention with paired ttest/Wilcoxon signed rank test.Result: A total of 89 participants were enrolled, 53 (59.5%) being male. Two-thirds of the participants were aged 20-39 years. During follow-up, 80 participants completed 12 weeks of yoga sessions. Post-intervention DASS-21 score decreased and WHO-5 increased significantly. The glycosylated hemoglobin (HbA1c) level and cholesterol-HDL ratio decreased significantly. Other variables didn't change significantly. No adverse effects were reported by the participants.Conclusion: Supervised structured yoga sessions helped decrease stress, depression, and anxiety and improved well-being. Therefore, it can be a feasible strategy to manage workplace-related stress and phycological morbidities.