This study uses data from the 2012 Aboriginal Peoples Survey to examine associations between the social determinants of health and two health outcomes among off-reserve First Nations, Métis and Inuit youth in Canada aged 12 to 18. The selected measures of health are excellent/very good health, and a diagnosed mood and/or anxiety disorder. Measures of socioeconomic status, the physical environment and the school environment were examined, including measures specific to the experiences of Indigenous peoples such as intergenerational trauma and cultural continuity. Findings show that a distinctions-based approach to quantitative research about Indigenous peoples is crucial, as associations between health and the social determinants differ by Aboriginal identity group and by health outcome. This study indicates that a wholistic and historical understanding of colonization is crucial for understanding outcomes, and a social determinants approach shifts the focus from individual behaviour to an examination of the structural barriers to good health.