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