The concept of inclusion is based on the assumption that integrating students with SEN into regular (mainstream) classes would enhance students’ performance due to a more stimulating and demanding environment. However, research investigating the effects of inclusive education on students’ academic self-concepts has been scarce. For this reason, the present study aimed to examine the specific relationships and differences for math and verbal self-concepts, self-esteem, and self-perceptions of social integration using two samples of elementary school students from grades 2–4: One group of students attended inclusive classes (n = 178), whilst the other group attended mainstream classes (n = 188). In addition, measurement invariance across classroom setting and possible mediator effects of self-esteem were tested. Results provided support for strong invariance across classroom setting. All constructs were positively correlated with each other. In both math and verbal domains, self-esteem and self-perceptions of social integration proved to be significant predictors of academic self-concepts. Self-esteem was more highly pronounced in younger children, while there were no effects of classroom setting on academic self-concepts. Self-esteem became a significant mediator of the relationships between self-perceptions of social integration and academic self-concepts. No group differences in math and verbal self-concepts, self-esteem, and self-perceptions of social integration were evident.