Purpose: The possibility of interaction between physical and mental fatigues was investigated in this study. Should any interaction between the physical and psychological fatigue takes place, it must accompany the changes in the brain. Therefore, the level of central activation ratio (central fatigue) has been measured as a function of monetary reward to elicit the extrinsic motivation. Methods: Twenty four healthy young male subjects performed quadriceps isotonic extensions until they experience the muscular fatigue. Then, the notification of the monetary reward depending on the level of extension force for the next 3 attempts were given to the experimental group, while no such information was given to the control group. During these post-fatigue isometric maximum voluntary contraction trials, the transcranial magnetic stimulation was delivered on the motor cortex to measure the central activation ratio. Two-way repeated ANOVA were performed. Results: Pre- vs. Post-fatigue comparisons confirmed that the subjects regardless of the group experienced the peripheral fatigue although the level of peripheral fatigue was less pronounced in the group with extrinsic motivation. On the other hand, the central activation ratio of the extrinsic motivation group did not displayed any decrease as the control group did. Conclusion: The results from this study provided an evidence showing the effects of motivation on the muscular fatigue. What’s intriguing is, however, the level of fatigue at the brain level showed no significant sign of fatigue when the monetary reward was suggested. It is presumable to suggest that the high motivation made our subjects prone to the central fatigue, and such effects might have decrease the peripheral muscle fatigue in turn.