The aim of this study was to explore the mechanism on perceived exertion during muscle fatigue. A total of 15 individuals in the fatigue group and 13 individuals in the nonfatigue group were recruited into this study, performing 200 intermittent handgrip contractions with 30% maximal voluntary contraction. The force, surface electromyography (sEMG), movement-related cortical potentials (MRCPs), and rating perception of effort (RPE) were combined to evaluate the perceived exertion during muscle fatigue. The maximal handgrip force significantly decreased (P<0.01), the root mean square of sEMG over each block significantly increased (P<0.01), and SD of force at plateau increased (P<0.01) during muscle fatigue. The RPE scores reported by the individuals and the motor potential amplitude of MRCPs in the fatigue group significantly increased (P<0.001). However, as for the individuals in the nonfatigue group, the other indexes showed no significant changes except for a little increase in the RPE. The within-subject correlation coefficients showed that there were significant correlations between RPE and motor potential amplitude of MRCPs at the C1 site (r=−0.609, P<0.001) and between RPE and root mean square of sEMG (r=0.541, P<0.001). Our results substantiate that the perceived exertion correlates with the central motor command during movement execution rather than the preparatory process. The perceived exertion not only reflects central fatigue but could also reflect the peripheral local muscle fatigue.