OBJECTIVE: Numerous studies have linked vitamin D to health-related quality of life (hrQoL) in chronically ill adults or elderly subjects. The aim of this study was to evaluate the association between 25-hydroxyvitamin D (25(OH)D) and hrQoL in a population-based sample of German adolescents. METHODS: A total of n = 5066 study participants from the nationwide, representative German Health Interview and Examination Survey for Children and Adolescents (Kinder- und Jugendgesundheitssurvey) aged 11-17 years were included in this post hoc analysis. HrQoL was measured using the well-validated self- and parent-rated Children’s Quality of Life questionnaires (KINDL-R), while the level of distress was assessed using the self- and proxy version of the Strengths and Difficulties Questionnaire (SDQ). Serum 25(OH)D concentrations were determined using a commercially available chemiluminescence immunoassay. RESULTS: Bivariate analyses demonstrated a significant positive association between 25(OH)D and hrQoL for both self- [estimate (E) = 0.82, 95 % confidence interval (95 % CI) 0.35-1.30, p = 0.001] and parent ratings (E = 1.33, 95 % CI 0.83-1.83, p < 0.001). In addition, we found negative correlations between 25(OH)D and self- (E = -0.34, 95 % CI -0.58 to -0.11, p = 0.005) and parent-reported total SDQ scores (E = -0.70, 95 % CI -1.03 to -0.37, p < 0.001). Generalized linear models adjusted for age, sex, body mass index, systolic blood pressure, migration background, socio-economic status, and sedentary screen time confirmed that 25(OH)D independently and significantly predicted better hrQoL (p = 0.004). CONCLUSIONS: These findings linking 25(OH)D to better well-being in a nationally representative sample of German children and adolescents suggest beneficial effects of vitamin D on mental health. However, recommendations for vitamin supplementation in healthy children and adolescents are not warranted from our data.