This cross-sectional study aims to shed further light on the relation between self-esteem and Eating Disorders (EDs) as part of prevention efforts by testing the mediating role of psychological inflexibility in a sample of young teenagers. Four hundred and eighteen Greek-speaking students from one representative public middle school in Cyprus (43.90% males and 56.10% females; M[subscript age] = 13.71, SD = 1.00) were screened for ED pathology using the Eating Attitudes Questionnaire-26 (EAT-26) and completed the Rosenberg Self-Esteem Scale (RSE) and the Avoidance and Fusion Questionnaire for Youth (AFQ-Y8). Screening was part of a school-wide psychoeducational Campaign titled "Love Your Body-Young Teens", which aimed to raise awareness on healthy body image and EDs within the school community. Correlations and bootstrapping mediation analyses were conducted to evaluate the relations between ED pathology, self-esteem, and psychological inflexibility. Mediation analyses results showed that psychological inflexibility partly mediates the relationship between self-esteem and ED pathology. These preliminary findings highlight the contributions of both the individual's negative internal events and their meta-response to these events in the development of EDs. It lays the foundation for the delivery of research-informed psychological prevention efforts in the schools, aiming to increase psychological flexibility among students.