Background: Muscle fatigue has been known to influence brain activity, but very little is known about how cortical centers respond to muscle fatigue. Objective: This study was conducted to investigate the effects of muscle contraction and fatigue induced by two different percents of maximal voluntary contraction (MVC) on Electroencephalography (EEG) signals. Material and Methods: In this quasi-experimental study, EEG signals were recorded from twenty-one healthy human subjects during three phases (rest, pre fatigue and post fatigue) contraction of Adductor pollicis muscle (APM) at 30% and 70% MVC. The mean powers of EEG bands (alpha, beta and gamma) were computed offline in the frequency domain. Results: None of the three phases with each percent of MVC revealed significant differences for all bands (p>0.05). Comparison of two hemispheres showed that right hemisphere gamma band activity was enhanced during pre-fatigue state at 30% MVC (p= 0.042) and post-fatigue state at 70% MVC (p= 0.028). Right hemisphere beta band activity also increased prominently at 70% MVC in post-fatigue condition (p = 0.030). Conclusion: These results suggest muscle contraction and fatigue at 30% and 70% MVC have no significant effect on EEG activity, but the trends of beta and gamma band activities are almost similar in each percent of 30% and 70% MVC. Right brain hemisphere shows more activity than left hemisphere in beta and gamma rhythm after fatigue state at 70% MVC.