Rejection sensitivity (RS) is a cognitive and affective disposition to defensively expect, perceive, and overreact to signs of rejection by others. The current study examined the role of RS as a mediating mechanism underlying the relation between school relations with peers and teachers and solitude in early adolescence. Italian middle school students (N = 656; females = 50.9%; X[bar][subscript age]=12.24) reported their RS, quality of relationships with their friends and teachers, peer-related loneliness, and attitudes toward aloneness. The results showed direct associations between school relations and RS components, as well as between RS and the three dimensions of solitude. Moreover, structural equation models showed that anxious RS and RS expectations, but not angry RS, mediated the association between school relations and solitude. The present study contributes to our understanding of the key mechanisms underlying the association between school relations and solitude.