OBJECTIVES. Musculoskeletal pain is a common complaint in a pediatric health care practice, but exercise tolerance has never been described in detail in these children. Our objectives for this study were to evaluate the maximal exercise capacity, including peak heart rate and oxygen consumption, of children with pain-related musculoskeletal problems, particularly in children with (symptomatic) generalized joint hypermobility and hypomobility, during a bicycle ergometry test to exhaustion; to evaluate muscle strength, bone mineral density, and sports activities in these children and to associate these observations with exercise capacity; and to compare these results with reference values. METHODS. Thirty-two children (mean age: 12.1 years; SD: 3.4 years; range: 6.2–20.1 years; 62% male) with musculoskeletal pain–related syndromes (joint hypermobility syndrome [n = 13] and joint hypomobility syndrome [n = 19]) participated. The reference group consisted of 117 healthy primary school prepubertal children, 167 healthy secondary school adolescents, and 98 young adults (249 girls and 133 boys; mean age total reference group: 14.5 ± 4.0 years; range: 8–20.8 years). Anthropometry, range of joint motion, muscle strength, bone mineral density (speed of sound and broadband ultrasound attenuation), sports activities, and a maximal exercise test using an electronically braked cycle ergometer were performed, and the patient stopped because of volitional exhaustion. Expired gas analysis and heart rate and transcutaneous oxygen saturation by pulse oximetry measurements also were performed. RESULTS. Children with joint hypomobility syndrome as well as children with joint hypermobility syndrome had a higher mean z score (SD) of weight and BMI compared with the reference group. A significantly decreased absolute peak oxygen consumption and relative peak oxygen consumption in both patient groups was found compared with control subjects. In 14 of 32 children with a z score relative peak oxygen consumption of less than −2, maximal heart rate was significantly decreased compared with 18 children with a z score relative peak oxygen consumption of −2 or more (mean [SD] z score speed of sound: −1.3 [0.8] vs −0.5 [1.0] and mean [SD] heart rate: 175.9 [11.5] vs 187.5 [10.9], respectively). In the total group, a high significant correlation between the z score of relative peak oxygen consumption and the z score of the speed of sound was found as well as with z score of BMI. Sixteen (50%) of 32 participated in sports activities with (mean: 0.9 hours/week; SD: 1.4 hours/week), whereas in the control group, 12% of did not participate in sports activities (mean: 2.8 hours/week; SD: 2.2 hours/week). Children who participated in sports activities had a (borderline) significant increased mean (SD) z score of absolute peak oxygen consumption and mean (SD) z score of broadband ultrasound attenuation compared with children who did not participate in sports activities (−0.3 [1.1] vs −1.2 [1.3] and −0.45 [0.8] vs −0.9 [0.5], respectively). CONCLUSIONS. In children with musculoskeletal pain–related syndromes, particular in children with (symptomatic) generalized joint hypermobility and hypomobility, maximal exercise capacity is significantly decreased compared with age- and gender-matched control subjects. The most probable explanation for the reduced exercise tolerance in our patients is deconditioning.