Sexual minority populations experience disparities in health outcomes. However, the mechanisms by which these disparities exist are understudied. The primary objective of this study was to examine the relationships between sexual orientation and health-related quality of life outcomes (HRQOL): self-rated health, mental distress, and physical distress. Additionally, structural discrimination was tested as an effect modifier in these relationships. Data for this study came from the 2016 Behavioral Risk Factor Surveillance System (BRFSS). Logistic regression models were used to compare HRQOL outcomes by sexual orientation and structural discrimination, controlling for sociodemographic characteristics. Overall, 3.3% (n=6,264) of the study sample (N=191,591) identified as lesbian, gay, or bisexual. Compared to heterosexual women, bisexual women reported significantly greater adjusted odds of all adverse HRQOL outcomes (p<0.001). Lesbian women also reported greater adjusted odds of adverse HRQOL outcomes, though results were only significant for frequent mental distress (p=0.007). Compared with heterosexual men, gay and bisexual men had significantly greater adjusted odds of frequent mental distress (p<0.001), and bisexual men had significantly greater adjusted odds of fair/poor self-rated health (p=0.034). Bisexual men and women had higher weighted prevalence of adverse HRQOL outcomes than gay men and lesbian women, respectively. Weighted prevalence rates of adverse HRQOL outcomes were greater among participants living in states with higher structural discrimination compared to their same-gender and sexual orientation counterparts in states with lower structural discrimination, regardless of gender or sexual orientation. However, structural discrimination was not found to have an overall modification effect in the relationships between sexual orientation and HRQOL outcomes. These findings contribute to the body of literature identifying health disparities among sexual minority populations. While prevalence of adverse HRQOL outcomes is lower in states with less structural discrimination, more research is needed to understand these mechanisms and identify other important stress processes that contribute to health disparities among sexual minority populations.