Materials and Methods: This cross-sectional study was performed on 419 overweight and obese female high school students of Kermanshah in 2017 selected through two-stage cluster sampling. Data were collected using the standard questionnaires, including high school students' academic performance, Rosenberg Self-Esteem Scale, Goldberg's General Health Questionnaire, Littleton's Body Image Concern Inventory, physical activity subscale of Walker's Health-Promoting Lifestyle Profile II, and Pittsburgh Sleep Quality Index. Data analysis for structural equation modeling was performed using the IBM SPSS AMOS V. 21 software. Results: Self-esteem was found to have significant direct (β=0.412) and indirect (β=0.142) effects on academic performance, with direct effects being stronger (P<0.001). Body image, physical activity, general health, and sleep quality were found to have a significant direct effect on academic performance (P<0.05). However, these factors also had a significant indirect effect on this variable through the mediation of general health (P<0.05). Overall, these variables accounted for 35% of the variance in academic performance. Conclusion: Self-esteem, body image, physical activity, and sleep quality affect the academic performance of obese and overweight girl high school students not only directly but also indirectly through general health. The results of this study demonstrated the mediating role of mental health in predicting the academic performance of overweight and obese girl students.