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Purpose. To compare physical fitness according to dimensions of Health-related Quality of Life (HrQOL) in Brazilian adolescents. Methods. A cross-sectional study of 588 adolescents (263 female) aged 12 to 17 years from a private school in Londrina, Paraná, Brazil. HrQOL was assessed by the Kidscreen-52 questionnaire. Four components of physical fitness were assessed: adiposity (sum of tricipital and subscapular skinfolds), muscular strength (handgrip test), flexibility (sit-and-reach test), and cardiorespiratory fitness (20m Shuttle run test). Differences in physical fitness across terciles of HrQOL were assessed using Analysis of covariance. Results. Adolescents with higher scores (3 rd Tercile) of HrQOL in the physical well-being dimension presented higher cardiorespiratory fitness and lower skinfold thickness (p < 0.05) compared to adolescents with lower scores (1 st Tercile). Those with higher scores in psychological well-being and social support and peer relation dimensions also presented lower skinfold thickness (p < 0.05). Performance in handgrip strength and flexibility did not differ across terciles of HrQOL in any dimension analyzed (p > 0.05). Conclusions. Adiposity and cardiorespiratory fitness seem to contribute to the physical well-being dimension of HQOL in Brazilian adolescents. Furthermore, adiposity also contributes to psychological well-being and social support and peer relations. Adiposity and cardiorespiratory fitness should be monitored to avoid low HrQOL in Brazilian adolescents.