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Background: A significant factor associated with well-being and health is to find a method which can increase resilience during the pandemics. The present research aimed to examine the impact of physical activity level on resilience of teenage girls during the COVID-19 pandemic with an emphasis on self-esteem as a mediator. Methods: The present study utilized a descriptive-correlation approach. The statistical sample included 384 teenage females from Golestan, Iran, in 2020. We employed standard surveys for collecting the data. Statistical methods included Kolmogorov- Smirnov test, Spearman correlation test, and structural relationships through Lisrel. Results: Physical activity was found to affect resilience (β=0.396, T=6.284) and self-esteem (β=0.628, T=11.594). Furthermore, self-esteem significantly affected resilience (β=0.530, T=9.509). Finally, self-esteem significantly mediated the correlation between physical activity and resilience (Z=6.780, p <0.001). Conclusions: Physical activity could be considered as an important factor in coping with severe condition during the COVID-19 pandemic. Therefore, in a pandemic situation, by increasing physical activity, better conditions can be created for children and adolescents, especially girls, to ensure their resilience.