The influence of creatine supplementation on substrate utilization during rest was investigated using a double-blind crossover design. Ten active men participated in 12 weeks of weight training and were given creatine and placebo (20 g/d for 4 d, then 2 g/d for 17 d) in two trials separated by a 4-week washout. Body composition, substrate utilization, and strength were assessed following week 2, 5, 9 and 12. Maximal isometric contraction (1-RM) leg press increased significantly (P < 0.05) following both treatments but 1-RM bench press was increased (33 kg ± 8, P < 0.05) only following creatine. Total body mass increased (1.6 kg ± 0.5, P < 0.05) after creatine but not after placebo. Significant (P < 0.05) increases in fat-free mass were found following both creatine (1.9 kg ± 0.8) and placebo (2.2 kg ± 0.7) supplementation. Fat mass did not change significantly with creatine, but decreased after the placebo trial (-2.4 kg ± 0.8, P < 0.05). Carbohydrate oxidation was increased by creatine (8.9% ± 4.0, P < 0.05), while there was a trend for increased RER after creatine supplementation (0.03 ± 0.01, P = 0.07). Changes in substrate oxidation may influence the inhibition of fat mass loss associated with creatine following weight training.