Burn survivors are at risk of developing post-traumatic stress disorder (PTSD) as a result of the traumatic event of a burn injury. In previous studies, burn-related variables such as burn severity were mainly studied as factors affecting the development of PTSD in burn survivors, while interest in psychological factors was limited. Pain interference and perceived stigma following severe burn injuries can act as psychological factors that remind burn survivors of their trauma and cause stress. This study aimed to investigate the role of pain interference and stigma in the relationship between burn severity and PTSD in burn survivors. A group of 483 burn survivors aged 18 years or older, registered in the Burn Model System Database, completed total body surface area (TBSA) measurements and a self-report inventory (Post-Traumatic Stress Disorder-DSM-V [PCL-5], PROMIS-29 Pain Interference Item SF, Neuro-QOL Stigma SF). Structural equations were performed to analyze the relationship between variables, and results showed that pain interference (p < .01) and stigma (p < .05) significantly mediated the relationship between burn severity and PTSD, respectively. This suggests that psychological variables such as pain interference and stigma, in addition to burn severity, have a significant impact on the development of PTSD in burn survivors. Additionally, the direct effect of burn severity on PTSD was not significant, but a fully mediated model revealed a significant serial mediating effect of pain interference and stigma (p < .01). This study’s findings suggest that post-burn pain and stigma can play a crucial role in affecting PTSD in burn survivors than the severity of the burn itself. This study expanded previous research on PTSD in burn survivors by revealing the complex mechanism by which burn severity leads to PTSD through pain interference and stigma.