Introduction: Adults with complex congenital heart disease show reduced aerobic exercise capacity and impaired skeletal muscle function compared to healthy peers. Peripheral muscle factors are presumed to be important contributors, but the mechanisms are poorly understood. Hypothesis: Muscle oxygenation is associated with reduced skeletal muscle endurance in adults with complex CHD. Methods: Sixty-four adults with complex congenital heart disease (mean age 36.9±14.8 years, females n=19) were recruited from centers specialized in congenital heart disease. Seventy-four age and gender matched healthy peers were recruited as controls. Muscle oxygen saturation was successfully determined on the anterior portion of the deltoid muscle using near-infrared spectroscopy for 57 patients and 71 controls. Measurements were made at baseline, during isotonic shoulder flexions (0-90°) to exhaustion and during 60 seconds of recovery. Results: The adults with complex CHD performed fewer shoulder flexions (38±15 vs. 69±40, p <0.001), had lower muscle oxygen saturation at rest (58±17% vs. 69±18%, p <0.001), a slower desaturation rate at exercise onset (-9.5±5.9%/sec vs. -15.1±6.5%/sec, p <0.001), and a slower resaturation rate post exercise (3.9±2.8%/sec vs. 5.4±3.6%/sec, p =0.008) compared to the controls. Conclusions: A distinct association was found between muscle oxygenation kinetics and early muscle fatigue for adults with complex CHD. Our findings may give insight to the underlying mechanisms for the reduced aerobic exercise capacity for these patients, and therefore provide implications for design of exercise training protocols in this population. [ABSTRACT FROM AUTHOR]