Khawajasira is a general terminology used typically in Pakistan that refers to the people who are transgender, hermaphrodite, inter-sexed, eunuch, transvestites, homosexual or bisexual (Brettell & Sagen, 1997). The current study examines the impact of Social Support and Self-efficacy in producing Psychological distress among Khawajasiras. A sample of total two hundred Khawajasiras (N=200) was drawn from the KhawajaSira community living in Southern Punjab. Urdu versions of Psychological Distress Scale K10 by Kessler (2010), General Self-Efficacy Scale (2003) and a 3 item self-created questionnaire were used to measure Psychological distress, Self-efficacy and Social support respectively. To measure reliability of all three scales, reliability analysis was performed. Analysis of data through SPSS suggested significant positive association among Self-efficacy and Social support; Social support and Self-efficacy significantly negatively associated with Psychological distress. Moreover, Social support significantly predicted the Psychological distress in Khawajasiras even after controlling the demographic variables. In KhawajaSira community, association between Social support and Psychological Distress was mediated by Self-efficacy. Suggestions for future research and implications of the study were also discussed.