Madsen, M, Larsen, MN, Cyril, R, Møller, TK, Madsen, EE, Ørntoft, C, Lind, RR, Ryom, K, Christiansen, SR, Wikman, J, Elbe, AM, and Krustrup, P. Well-being, physical fitness, and health profile of 2,203 Danish girls aged 10–12 in relation to leisure-time sports club activity—with special emphasis on the five most popular sports. J Strength Cond Res XX(X): 000–000, 2020—This study investigated the relationship between leisure-time sports club activities and well-being as well as physical health parameters in 10–12-year-old Danish girls. Two thousand two hundred three girls took part in the study, which included questionnaires on participation in leisure-time sports clubs, well-being, Yo-Yo intermittent recovery level 1 children's test, long jump, balance tests, body composition, blood pressure (BP), and resting heart rate (RHR). Data were analyzed according to whether the girls participated in leisure-time sport and according to the 5 most frequently reported sports. Girls enrolled in leisure-time sports had higher physical well-being (49.3 ± 8.6 vs. 45.2 ± 8.3), psychological well-being (50.4 ± 9.0 vs. 49.4 ± 9.8), experienced more peer and social support (50.2 ± 10.0 vs. 48.9 ± 10.7), and perceived a more positive school environment (52.5 ± 8.0 vs. 50.5 ± 9.3), as well as showing higher Yo-Yo (+39%), long jump (+10%), and balance performance (+15%) than girls not involved in sport clubs. The girls active in sports clubs had higher relative muscle mass (+5%), lower fat percentage (−11%), body mass index (−5%), RHR (−3.4 b·min−1), and diastolic BP (−1.4 mm Hg) compared with girls not involved in sport (p < 0.05). Girls who played soccer showed higher aerobic fitness compared with inactive girls (+67%), dancers (+39%), swimmers (+38%), and gymnasts (+16%). Gymnasts had a lower fat percentage than inactive girls (−19%), team handballers (−10%), swimmers (−12%), and soccer players (−4%). Girls participating in club-based leisure-time sports showed higher well-being and better fitness and health profiles than girls not involved in any sports club activities. Girls involved in soccer had better aerobic fitness and gymnasts a lower fat percentage.