Physical appearance comparisons (PAC) and social physique anxiety (SPA) have been independently related to disordered eating (DE). However, the extent to which these variables may be concurrently associated with DE in the adolescent population remains largely unknown. This study was aimed at addressing a twofold objective: firstly, to examine whether SPA may moderate or mediate the relationship between PAC and DE in a sample of Spanish adolescents of both sexes; secondly, to examine whether these mechanisms may differ according to sex. A total of 738 adolescents (50% girls) ranging from 12 to 17 years of age (M = 14.45, SD = 1.50) were recruited from nine secondary schools. Participants completed a self-reported questionnaire covering the variables of interest. After controlling for the effects of sex, age, standardized body mass index (z-BMI), and depressive symptoms, the results from bootstrapping cross-sectional regression analyses supported the mediating effect of SPA on the relationship between PAC and DE, but not the moderating one. Sex was not found to moderate either the mediated or moderated relationships. Prevention/intervention efforts targeted towards decreasing DE among adolescents may benefit from minimizing the social relevance of the body inherent in the cognitive and affective processes underlying both SPA and PAC.