Historically women have been underrepresented in the fields of science, technology, engineering and mathematics (STEM). Some scholars have suggested that science self-concept perceptions have contributed to this gender gap. We propose and empirically examine a model of the relationships between gender, sexual orientation, science self-efficacy, and science identity. Specifically, we hypothesise that a key explanation for why gender differences in science identity exist may be that science self-efficacy is intervening in the relationship between gender and science identity. Surveys were administered to 964 first-year university students in the U.S. Science self-efficacy mediated the relationship between gender and science identity for heterosexual students, but not for non-heterosexual students. Whereas external factors that may affect gender differences in science self-concept perceptions should be considered, such as boosting females' participation in science courses, the internal self-concept perceptions that individuals use to make decisions about STEM are of particular importance. Our results help to provide a better understanding of the roles that gender and sexual orientation play in science self-efficacy and science identity, and we hope that a better grasp of these relationships offers a step toward addressing the projected shortage of STEM workers.