Academic burnout has many consequences and can have adverse effects on the educational system of the country. The purpose of this study was to investigate the relationship between the students’ academic stress, stress response and academic burnout with the mediating role of self-efficacy. To this end, a total of 361 students (177 females and 184 males) was selected through multi-stage cluster sampling method and responded to Maslach Academic Burnout Questionnaire, Sherer General Self-Efficacy Questionnaire and Gadzella Student- Life Stress Inventory. The proposed model was evaluated through the structural model algorithm, using Imus Software. Mediating relationships were tested in the proposed model using the bootstrap method. Findings showed that the proposed model was well fitted with the data. Academic stress and stress response had a positive and significant effect on the academic burnout. The findings also showed that self-efficacy had a negative and significant effect on academic burnout. The results of indirect relationships showed that academic stress and stress response had a significant indirect effect on the academic burnout via self-efficacy. Overall, the results indicated that self-efficacy had a mediating role in the relationship between the academic stress, stress response and academic burnout.