Medical students are prone to burnout due to high volume and stressful courses and also attending medical centers. Therefore, the present study aimed to investigate the relationship between self-esteem and field of study and its effect on academic burnout in students of Shiraz University of Medical Sciences. This cross-sectional study was conducted on 600 students of Shiraz University of Medical Sciences selected by multi-stage cluster sampling in 2018. Data were analyzed by SPSS (R) software. The mean score of self-esteem in men was higher than that of women and the mean score of burnout in men was lower than that of women, but this difference was not statistically significant. There was no significant difference in the mean of self-esteem among single and married students. Also, the level of academic burnout was significantly lower among married students than single students. There was a significant negative correlation between self-esteem and academic burnout. The results of the regression analysis showed that academic burnout is the only predictor of student self-esteem. The precise and principled planning for medical and paramedical students who are prone to severe academic burnout due to their very difficult educational situation can play an important role in increasing self-esteem in these student