BACKGROUND: Health professionals are burn out syndrome prone occupational group. In Ethiopia there are limited evidences about burnout syndrome and work related determinant factors resulting in Burnout syndrome. Therefore, this study aimed to determine the prevalence of burnout syndrome and associated factors of burnout syndrome among health professionals working in university hospitals found in Sidama region and Southern Ethiopia 2023. METHODS: An institution based multi-center cross-sectional study was conducted on 362 health professionals working in three university hospital from February 15 to February 30, 2023. Study participants were recruited using Simple random sampling technique. A standard self-administered Maslach Burn out Inventory questionnaire were used to collect data. Data entered into Epi-info version 7.2.5.0 and exported to stata version 17 for analysis. Multivariate logistic regression was used to identify factors associated with burnout syndrome and adjusted odds ratio with a 95% confidence interval were used to describe factors associated significantly. Variables with a P value of less than 0.05 were considered statistically significant. RESULT: A total of 362 health professionals were enrolled in the study with a response rate of 100%. The prevalence of burnout syndrome among health professionals was found to be 198 (54.7%) with a 95% CI of 49.51-59.77%. Alcohol dependence (AOR = 6.41, 95% CI = 2.37- 17.29), Sleep problem (AOR = 3.88, 95% CI = 2.33-6.46), poor social support (AOR = 4.71, 95% CI = 2.21-10.01) and intermediate social support (AOR = 2.41, 95% CI = 1.07-5.42) were factors significantly associated with burnout syndrome. CONCLUSION: This study revealed that a high proportion of health professionals working in university hospitals of sidama and southern part of Ethiopia suffer from burnout syndrome. Alcohol dependence, sleep problem, getting poor and intermediate social support were significantly associated predictor variable with burnout syndrome. RECOMMENDATION: Higher officials of university hospitals and human resource department should design strategies to reduce alcohol dependence, promote healthy sleep habit and advocate strong social support among health professionals.