During the course of sexual development, many people experience dissonance between dimensions of sexual orientation, including attraction, behavior, and identity. This study assesses the relationship between sexual orientation discordance and mental health. Data were obtained from the National Longitudinal Study of Adolescent to Adult Health (n = 8,915; female = 54.62 %; non-Hispanic black = 18.83 %, Hispanic = 14.91 %, other race (non-white) = 10.79 %). Multivariable linear regression evaluated the correlation between sexual orientation discordance and perceived stress and depressive symptomatology. Models were stratified by sex and sexual identity. Among self-identified heterosexual females and mostly heterosexual males, sexual orientation discordance predicted significantly increased depressive symptomatology. No other subpopulation demonstrated a significant correlation between sexual orientation discordance and depressive symptomatology or perceived stress. The association between sexual orientation discordance and depressive symptomatology suggests a link between sexuality, self-concept, and mental health.