Introduction: Although stigma of substance abuse and its impact on psychological health have recently received considerable attention, these problems are under-addressed among Arab patients. Aim: This study aimed to investigate stigma, psychological distress, and their correlates among Egyptian substance users. Methods: This cross-sectional study involved a convenient sample of 149inpatient substance users (142 males, mean age= 32.5 years, SD= 6.8 years, range: 19-60 years).They completed the Self-Stigma in Alcohol Dependence Scale and the Depression Anxiety Stress Scale-21. Hierarchical multiple regression was conducted to identify correlates of stigma and psychological distress. Results: In adjusted analysis, young age, abuse of alcohol and Bango were significantly associated with stigma. Shame and shorter hospital stays were associated with higher psychological distress, explaining 31% of the variance, and bait along with stereotype agreement explained 36% of the variance in depression scores. Discussion: Younger substance users are more likely to internalize stigma. Meanwhile, the shame component of internalized stigma has the worst effect on psychological health. Implications for practice: The findings necessitate stigma interventions that target shame reduction to enhance the psychological well-being and recovery of substance users.