This study was a novel exploration of psycho-social and neuroendocrine factors that may contribute to mental health in LGB youth and young adults. Research suggests that, compared to their heterosexual peers, LGB youth and young adults report alarmingly elevated rates of depression, anxiety, suicidal ideation and attempts, and lower self-esteem in concert with a much higher incidence of victimization from family and peer-groups. Homophobic societal attitudes compounded with discrimination, marginalization, stigma, and victimization experienced by LGB individuals are thought to contribute to the development of internalized homonegativity (IH) and psychological distress. Research also suggests that victimization and social stressors can dysregulate cortisol activity, leading to increased risk for mood disorders. The main goal of the present study was to investigate the interplay of bio-psycho-social factors that are thought to contribute to positive and negative indices of mental health in a community sample of 63 LGB young adults in Montreal, Canada. Dysregulated diurnal cortisol activity and internalized homonegativity were postulated to function either as mediators or as moderators of the links between parental support, social support and LGB-related stress on the one hand, and depression, anxiety, suicidality and self esteem on the other. LGB young adults experiencing more LGB-related stress had more depressive symptoms and lower self-esteem. Interaction effects with parental and social support were also found. IH and cortisol were both positively correlated with LGB-related stress. IH and cortisol slope jointly predicted depression, but each uniquely predicted the other measures of mental health. LGB young adults experiencing varying levels of IH benefited from different social relationships. Cortisol slope also moderated the relations between support, victimization and mental health. These results are particularly striking given the overall high-level of mental-health of this particular sample. The findings of this study were in accord with diathesis-stress models of mental health. Implications for understanding the bio-psycho-social basis of mental health and promoting the well-being of LGB young adults were considered, as were limitations imposed by the sample and methodology.