Aboriginal people are vastly overrepresented in the HIV epidemic in Canada, but little is known about whether some Aboriginal groups are more at risk than others. The purpose of this paper is to highlight the differences in health and social determinants between First Nations, Metis and Inuit Aboriginal people living with HIV/AIDS in Ontario. Eighty Aboriginal people living with HIV/AIDS living off of reserve were recruited and interviewed by trained peer research assistants to collect information on socio-demographics, health status, housing, health care access, homelessness, discrimination, and health-related quality of life. Fifty (63%) participants were First Nations who would have lived at least part of their lives in reserve communities and 30 (37%) were Metis and Inuit who have lived most of their lives off of reserve settings. Our findings indicate that all Aboriginal people are coping with severe health and social stresses that threaten their health. However, First Nations people were less likely that Metis and Inuit people to have completed high school, and they were more likely to have been incarcerated, to have been homeless, to not feel at home in their neighbourhood, to have harmful alcohol use, and to have experienced significant depression. First Nations people were also less likely than Metis and Inuit to be on antiretroviral treatment or to have seen an HIV specialist. More research is required to determine to what extent conditions on reserve (e.g., little access to health care, AIDSphobia) and/or the loss of social support from leaving the reserve community contribute to the difference in health and social determinants between First Nations, Metis and Inuit people with HIV living off of reserve in order to develop more appropriate services in both reserve and non-reserve settings that will improve health of all Aboriginal peoples.