This study aimed to present a causal model for predicting post-traumatic stress disorder (PTSD) based on alexithymia and psychological distress, with the mediating role of defense styles in individuals with HIV. The research employed a descriptive-correlational design using structural equation modeling (SEM). The statistical population consisted of 2,000 individuals with HIV who had active medical records in 2023 at the Counseling Center of Imam Khomeini Hospital, Tehran. Based on the sample size formula and random sampling, 240 eligible individuals receiving antiretroviral medication were selected. Data were collected using the Post-Traumatic Stress Disorder Checklist (Weathers & Litz, 1994), the Toronto Alexithymia Scale (Bagby et al., 1994), the Kessler Psychological Distress Scale (2002), and the Defense Style Questionnaire (Andrews et al., 1993). Data analysis was conducted using path analysis and SEM via AMOS 26 software. The findings indicated that the proposed model had a good fit and that defense styles mediated the relationships between PTSD, alexithymia, and psychological distress. Given the unique psychological challenges and disease-related stress experienced by individuals living with HIV, these findings can help mental health professionals develop preventive and therapeutic interventions to reduce psychological harm and improve mental health outcomes in this population.