Background: Prior research has found that education's association with health can differ by social positions such as gender. Yet, none of the existing work has tested whether the relationship between education and self-rated health is equivalent across sexual orientation groups, and additionally, if these associations differ for men and women. Deploying the intersectionality perspective, we expand current debates of education as a resource substitution or multiplication to include sexual orientation. Methods: We answer these questions using data from the Behavioral Risk Factor Surveillance System (BRFSS), a probability-based sample of adults living in 44 US states and territories for selected years between 2011 and 2017 (n = 1,219,382). Results: Supporting resource multiplication, we find that compared to their same-gender heterosexual counterparts, education is less health-protective for bisexual adults, especially bisexual women. Gay men and lesbian women, on the other hand, seem to have similar associations of education with health as their same-gender heterosexual counterparts. Turning to gender comparisons across sexual identity groups, we find that resource substitution may operate only among heterosexual women when compared with heterosexual men. Conclusions: In sum, this study suggests that the relationship between education and health may depend on the intersection of gender and sexual orientation among U.S. adults.