The present study aimed to compare substrate oxidation and total energy expenditure during running with low and moderate intensity until exhaustion and one hour after exercise in obese male students. For this purpose, in a crossover study design, 11 male university students (mean age 20.45±1.69 years, BMI 31.26±1.3 kg/m2, body fat percentage 28.47±3.53 %) participated in this study. Two exercise protocols, running with low intensity (45% VO2max equivalent to 66% of maximum heart rate) and moderate intensity (60% VO2max equivalent to 76% of maximum heart rate) were performed on a treadmill with an 11-day interval. Subjects' respiratory gases were collected and analyzed 30 minutes before the exercise while subjects were in prostrate position and also during the low and moderate exercises till they reached the exhaustion level, and also one hour after exercise as EPOC. The amount of fat oxidation, carbohydrate and energy expenditure was measured by indirect calorimeter. The results showed that during the exercise, fat oxidation during moderate intensity exercise was significantly higher than low intensity exercise. However, in the total exercise there was no significant difference between the two intensities. There was no significant difference in carbohydrate oxidation during the exercise and in the total exercise between the two intensities. Also, in the total exercise, energy expenditure during low intensity exercise was significantly higher than moderate exercise. Accordingly, low intensity activities until exhaustion was preferred to lose weight in comparison with moderate activities until exhaustion. However, if we do not consider the time of the exercise, because the maximum of fat oxidation occurs during intensity close to moderate intensity, the exercise training with moderate intensity is more suitable for maximum of fat oxidation and weight loss.