Physical and mental health is vital for improving the quality of life of adolescents, which plays a significant role in their future development. The purpose of this study was to investigate the relationship between body mass index (BMI), physical fitness and self-esteem. The statistical population included high school students of Mashhad and Torbat-Heydarieh, 222 of them (108 girls and 114 boys) were selected by available sampling method. To collect data, BMI was calculated by dividing people's weight in kilograms by the square of height in meters, also physical fitness questionnaire and Rosenberg's self-esteem scale were completed. Data analysis was done through mean, Pearson correlation coefficient, and regression analysis using SPSS-26 software. The results showed that there is a negative and significant relationship between BMI and self-esteem in both boys and girls groups as well as in the whole sample (P<0.01). There was a negative and significant relationship between physical fitness and self-esteem in both groups and in the entire sample (P<0.05). The comparison of regression coefficients showed that in the group of girls, body mass index and physical fitness are negative and significant predictors for self-esteem, and body mass index has a greater contribution in predicting self-esteem. In boys, only body mass index (β=0.21) was a negative and significant predictor of self-esteem. In general, the findings showed that there was a negative and significant relationship between self-esteem, body mass index and readiness for physical activity in the whole sample and according to gender in adolescents, which indicates the necessity of designing interventions focused on physical and mental health, especially for girls.