Sport and physical exercise result in muscle fatigue. Fatigue could affect performance of sport. The purpose of this study was to examine the effect of muscle fatigue on the amplitude of ERPs and RT. Sixteen male college students participated in this study. ERPs were recorded at scalp site of Fz, F3, F4, Cz, C3, C4, Pz, P3, P4, T3, T4, T5, T6, O1, and O2 of the traditional 10-20 system. ERPs N1 and N2 were obtained at site O1 and O2, while ERPs P3 was obtained at site Pz. For the purpose of the current study, only the amplitudes of these ERPs components were analyzed. The experiment consisted of two conditions. At the control condition, participants were required to perform a discriminating RT task. At the fatigue condition, before performing a similar discriminating RT task as that of control condition, participants were required to squeeze a grip dynamometer up to the point that they couldn't follow the required pace and their maximum grip power was half of the pretest value. Paired t test was performed on the amplitude of N1, N2, P3, and RT separately. RT was faster at the fatigue condition than the control condition. The amplitude of N1 and P3 were decreased at fatigue condition. The results of the current study revealed that muscle fatigue have impact on individual's cognitive processes as indexed by ERPs and RT.