Muscle and strength loss will occur during periods of physical inactivity and immobilization. Creatine supplementation may have a favorable effect on muscle mass and strength independently of exercise. The purpose of this study was to determine the effects of creatine supplementation on upper limb muscle mass and muscle performance after immobilization. Before the study, creatine-naïve men (n = 7; 18-25 years) were assessed for lean tissue mass (dual-energy X-ray absorptiometry), strength (1-repetition maximum [1RM] isometric single arm elbow flexion/extension), and muscle endurance (maximum number of single-arm isokinetic elbow flexion/extension repetitions at 60% 1RM). After baseline measures, subjects had their dominant or nondominant (random assignment) upper limb immobilized (long arm plaster cast) at 90 degrees elbow flexion. Using a single-blind crossover design, subjects received placebo (maltodextrin; 4 x 5 gxd-1) during days 1-7 and creatine (4 x 5 gxd-1) during days 15-21. The cast was removed during days 8-14 and 22-29. The dependent measures of lean tissue mass, strength, and endurance were assessed at baseline, postcast, and after the study. During immobilization, compared with isocaloric placebo, creatine supplementation better maintained lean tissue mass (Cr +0.9% vs. PLA -3.7%, p < 0.05), elbow flexor strength (Cr -4.1% vs. PLA -21.5%, p < 0.05), and endurance (Cr -9.6% vs. PLA -43%, p < 0.05), and elbow extensor strength (Cr -3.8% vs. PLA -18%, p < 0.05) and endurance (Cr -6.5% vs. PLA -35%, p < 0.05). These results indicate that short-term creatine supplementation attenuates the loss in muscle mass and strength during upper-arm immobilization in young men.