The purpose of this study was to investigate the effect of short term creatine monohydrate supplementation on baseline homocysteine concentrations and following an exhaustive exercise in active men. Twelve male students who were members of soccer team of Mazandaran University (age: 21.83±2.20 years, BMI: 13.53±58 kg/m2, Homocysteine: 13.53±58 ?mol/lit) volunteered to participate in this study. They were randomly divided into creatine monohydrate (n=6) and placebo (n=6) groups. After 12 hours of fasting, blood samples were gathered before and immediately after the exhaustive exercise. Each subject of the experimental group received creatine monohydrate (0.3 g/kg) for 5 days. After these 5 days of supplementation, blood samples were gathered before and immediately after the exhaustive exercise. Dependent and independent t-tests were used as the statistical method (P?0.05). Results showed that these 5 days of creatine monohydrate supplementation significantly decreased baseline plasma homocysteine (P=0.017), and following the exhaustive exercise (P=0.013). It appears that creatine monohydrate supplementation prevents the probable negative effects of homocysteine on health with a reduction in the baseline levels and following an exhaustive exercise.