ABSTRACT: BACKGROUND:Persistent pain has a high prevalence among adolescents. Pain has been shown to reduce all aspects of the adolescent's health-related quality of life (HRQOL). In adult patients with pain, self-efficacy has been shown to mediate the relationship between pain intensity, disability and depression. However, little is known about whether self-efficacy acts as a mediating variable in the relationship between persistent pain and HRQOL sub-scale scores in a school-based population of adolescents. OBJECTIVES:To describe the experience of pain, HRQOL and self-efficacy, and to explore the association between pain intensity, general self-efficacy and HRQOL in adolescents with persistent pain by testing self-efficacy as a possible mediator. METHODS:The study participants were 78 adolescents with persistent pain, aged 16-19?years, who were recruited from five high schools in southern Norway. All participants completed an electronic survey consisting of the Lubeck Pain Questionnaire, which included a visual analogue scale (VAS) measuring pain intensity, the General Self-Efficacy Scale (GSE) and the KIDSCREEN-52 Questionnaire measuring HRQOL. Statistical analyses were conducted using the PROCESS macro for SPSS developed by Andrew Hayes. RESULTS:All participants reported pain in multiple locations, of which the head was most common (88.5%). Mean (SD) pain intensity score of the participants was 5.4 (1.8). The study sample had poor HRQOL, with mean (SD) scores for several sub-scales ranging from 45.2 (21.0) to 91.0 (13.3) on a 0-100 scale. The associations between pain intensity and the HRQOL sub-scales of physical well-being, psychological well-being, mood, self-perception, autonomy and school environment were mediated by self-efficacy. The highest degree of mediation and, thus, the largest indirect effect was estimated for the HRQOL sub-scale physical well-being (67.2%). CONCLUSIONS:This school-based sample of adolescents with persistent pain had impaired HRQOL. Up to 67% of the reduction in the HRQOL sub-scale scores for physical well-being, psychological well-being, mood, self-perception, autonomy and school environment could be explained by the mediating variable self-efficacy. Thus, future pain-management interventions that aim to increase HRQOL in school-based populations of adolescents with persistent pain should consider promoting self-efficacy and providing more targeted interventions. TRIAL REGISTRATION:ClinicalTrials.gov ID NCT03551977.