BACKGROUND: Depression continues to be a public health crisis for young adults. For high school students, past research has identified trauma as a significant predictor of depression. Congruent with the theory of cumulative stress, the present study hypothesized that the effect of sexual assault on depression would be stronger among lesbian, gay, and bisexual (LGB) students than among their straight peers. METHODS: Using the Youth Risk Behavior Survey completed by students attending Duval County Public Schools in Florida (N = 3053), this study used secondary data analysis to conduct 2 regression analyses, one for boys and one for girls. RESULTS: LGB status was associated with 3-fold increase in the odds of reporting depression for both boys and girls. History of sexual assault was associated with a significant increase in reporting depression. There was also a significant interaction effect between sexual orientation and history of sexual assault among male students only (p <.05). Contrary to the hypothesis, the effect was stronger among straight boys than among LGB boys. CONCLUSION: Minority students continue to evidence greater risks for depression. Opportunities for systemic changes to address these include training teachers, banning conversion therapy, and implementing comprehensive sex education.