Introduction: Depression is a vital issue to be concerned about because it is anticipated to be one of the major health issues confronting Malaysia in the coming years. Social media has emerged as one of the main contributors to depression due to the increased use of technology in modern society. Therefore, this study aimed to investigate the association between social media use and depression among IIUM students. Methods: This cross-sectional study involved 227 students of IIUM Kuantan from three Kulliyyahs; Kulliyyah of Allied Health Sciences (KAHS), Science (KOS) and Dentistry (KOD). Convenience sampling was applied and self-administered questionnaires were distributed. Data was analysed using Statistical Package Software for Social Sciences (SPSS), where descriptive frequency table, Mann-Whitney U test, Kruskal-Wallis test and Correlation test were applied. Results: This study indicated that the level of social media-related depression among students in selected kulliyyah in IIUM Kuantan was low (n=61, 26.9%). Body image dissatisfaction, online harassment, sleep disturbance and high self-esteem were significantly associated with low depression. Socio-demographic factors, which are the types of kulliyyah and working part-time, were significantly associated with depression, with a p-value of 0.002 and 0.012, respectively. Conclusion: Social media use and depression were associated considerably, involving body image, online harassment, sleep, and self-esteem. A guideline and education for better and safe use of social media in our country should be proposed as part of preventive action in future.