Objective: To determine the association of self- esteem with stress levels among medical students and its contributing factors. Methodology A cross-sectional study was conducted at Liaquat Medical University Hospital, Jamshoro Sindh between [enter dates], for a duration of [enter months]. All students aged 18 or above were included in the study. The study hypothesised that those students having low self- esteem suffer from higher levels of stress compared to those with better self-esteem. The scales used for the study were “Rosenberg self-esteem” and “perceived stress scale”, along with detailed demographic information of all students. Descriptive statistics and cross-tabulation were applied using the Statistical Package for Social Sciences (SPSS, V.26). A p-value of < 0.05 was set as the cut-off value for significance. Results: The mean age of participants was 21.47 years (enter standard deviation) with a range between 18-28 years. Results indicated that students with a low level of self-esteem were more likely to have a high level of stress (70.8% vs 36.5%), whereas students with a reasonable level of self- esteem showed to have very less stress (17.5% vs 8.4%). However, those with a high level of self- esteem still have quite a high level of stress (46.0% vs 20.8%). Results from the study were indicating that although self-esteem has a considerable impact on developing stress levels as seen in low esteem students, may not always affecting in the same manner as in the case of high self-esteem students where students showed to have a high level of stress. Conclusion: The current study indicated that low self-esteem among medical student results in higher stress levels. Additionally, we found that the association of self-esteem is high in female than male, and it is significant in males.