Background: Creatine monohydrate (CrM) has been shown to be benefi cial to health due to its antioxidant potential. Strenuous exercise is associated with oxidative stress, which could lead to apoptosis. We investigated the ability of CrM in amelioration of apoptosis induced by incremental aerobic exercise (AE) to exhaustion in young athletes. Materials and Methods: In a placebo-controlled, double-blind, randomized, parallel study, 31 young athletes (age 19.52 ± 2.75 years, body mass 79.24 ± 16.13 kg, height 1.73 ± 6.49 m, body fat 16.37% ± 5.92%) were randomly assigned to CrM (4 × 5 g/day, n = 15) or placebo (PL: 4 × 5 g/day of maltodextrine powder; n = 16) to investigate the eff ect of 7 days CrM on serum p53 and insulin-like growth factor-1 (IGF-1) concentration after acute incremental AE test to exhaustion. Subjects performed AE before (test 1) and after 7 days of supplementation (test 2). Results: Before supplementation, AE to exhaustion induced a signifi cant increase in serum p53 and IGF-1 concentrations at both CrM and PL groups (P < 0.05). After supplementation, serum p53 concentrations were signifi cantly lower in CrM than PL at post-AE (P < 0.05). h ere were no diff erences in IGF-1 concentrations between CrM and PL groups at post-AE (P > 0.05). Conclusion: Our results suggest that supplementation with CrM prevents apoptosis, as measured by decreases in p53 concentration, induced by AE to exhaustion in young athletes. However, CrM had no eff ect on IGF-1 concentration after AE to exhaustion in young athletes.