Objective(s): In order to shed light on the impacts of various stressful life events and resilience factors during adolescence and across different cultural backgrounds, this study explored a variety of protective and vulnerability factors associated with psychological distress among Aboriginal and non-Aboriginal youth. Methods: The participants were 207 adolescents (mean age = 15.8 years, 55% female, 45% Aboriginal) recruited from two secondary schools located in Innu communities of Saguenay-Lac-St-Jean and Côte Nord (Canada). Data were collected on psychological distress, exposure to stressful life events, and resilience. Results: Six multiple linear regressions were conducted to predict six dimensions of psychological distress. Sexual abuse, family violence and other stressful life events were all associated with higher levels of psychological symptoms. Individual resilience factors were associated with lower levels of depression, anxiety, dissociation and post-traumatic stress (PTS), whereas relational/familial resilience factors were associated with lower levels of anger and sexual concerns. The relationship with contextual resilience was not significant. Conclusions and implications: Overall, these results indicate that stressful life events such as sexual abuse and family violence may have deleterious effects on the mental health of Aboriginal and non-Aboriginal adolescents. However, some individual and relational factors may have positive effects on their mental health. These findings may provide hope for communities under greater stress and support the importance of establishing culturally sensitive intervention strategies that strengthen the key protective factors identified in this study.