OBJECTIVES: Health care workers were exposed to huge stress during COVID-19 pandemic affecting their physical and mental health. Practice of anulom vilom pranayama and heartfulness meditation (AVPHFN) can improve mental and physical health and counter stress. The present study explored the effect of 8-week AVPHFN intervention on autonomic functions, emotional stress, oxidative stress, and inflammation markers in the nurse group of health-care givers. METHODS: This was a randomized controlled trial where 50 nurses underwent AVPHFN and 50 participated as controls. At baseline and after 8 week intervention of AVPHFN anthropometric parameters, cardiovascular parameters, autonomic function including time and frequency domain parameters, biochemical parameters, and psychological stress using the questionnaire were assessed. RESULTS: Forty nurses in AVPHFN group and 46 in control group completed the study. AVPHFN intervention resulted in a significant reduction in cardiovascular parameters heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure and rate pressure product (p<0.001, p<0.001, p<0.001, p<0.001, and p<0.001, respectively), perceived stress score and depression, anxiety, and stress scale psychological variables of depression, and stress compared to the control group. Total power, ratio of low frequency to high frequency and change in successive normal sinus (NN) intervals exceeds 50 ms (p<0.01, p=0.05, and p<0.01 respectively) suggesting parasympathodominance due to higher vagal efferent activity. Serum cortisol, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha, interleukin (IL)-1, IL-6 and telomerase significantly decreased in AVPHFN group post intervention. CONCLUSIONS: Eighty-week intervention of AVPHFN improved psychophysiological, autonomic and biochemistry profile of nurse group of health-care workers. AVPHFN module may be beneficial for curtailing stress and improving well-being.