The present study was conducted from June–July, 2021 in online mode and a questionnaire was designed at the Department of Food Science and Nutrition, College of Community Science, G. B. Pant University of Agriculture and Technology, Pantnagar. The study aims to find an association of perceived stress with socio-demographic factors, health profile and physical activity among Indian adults during the second wave of COVID-19. Data on perceived stress was collected through an online cross-sectional survey of 1933 Indian adults based on the Perceived Stress Scale (PSS). Multivariate ordinal regression was conducted to identify the predictors of perceived stress. Indian adults were moderately stressed, with a mean PSS score of 19.7±5.5 during the crisis time of COVID-19. The study population remained moderately active (59.3%) during the lockdown period. Perceived stress was negatively associated with age, education, income, and physical activity and positively associated with random blood sugar levels and sitting time. Odds of perceived stress increased with female gender, separated marital status, having one child or adolescent in the family, graduate or postgraduate as the educational status of the family’s head, and increased sitting time. High educational status, retirement, regular employment, middle or lower-class social class, and high physical activity level were negative predictors of perceived stress. The current investigation highlights the role of multiple factors in the perception of stress and the need for tailored interventions for vulnerable groups focusing on education and physical activity.