This study aimed to evaluate and report on the effects of HIV-related stigma on the psychological health of AIDS orphans. The study used a systematic review methodology to search electronic databases, including Academic Search Complete, SA ePublications, MEDLINE, PubMed, BioMed Central, CINHAHL and PsychARTICLES from January 2004 to September 2015. Inclusion criteria included: studies of a qualitative, quantitative or mixed methodology which focused on the effects HIV-related stigma of the psychological well-being of AIDS orphans, studies were required to be open access, peer reviewed, full text articles in English medium. The study extracted findings four systematic steps: (1) identification; (2) screening; (3) eligibility; (4) inclusion. The study used a meta-synthesis for the extraction and amalgamation of findings. Nine studies were included in the final review and showed consistent evidence of HIV-related stigma contributing to the increased level of psychological distress and poor mental functioning among AIDS orphans. This study was limited by low levels of disclosure among AIDS orphans and the omission of grey literature. However, it does shed light on the effects of HIV-related stigma on the psychological well-being of AIDS orphans.