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Purpose: The present study was designed to determine to what extent muscle damage induced by repetitive eccentric exercise with maximal voluntary effort (ECC) affects the time course of central and peripheral fatigue during sustained maximal voluntary contraction (MVC)., Methods: Ten healthy male volunteers were asked to perform brief (control MVC) and sustained MVC (fatigue test of 60 s in duration) with elbow flexion before and 2 and 4 d after ECC. Transcranial magnetic stimulation (TMS) was applied to the motor cortex to determine changes in voluntary activation (VA), the size of the motor evoked potential (MEP), and length of electromyographic (EMG) silencing. The ratio of the root mean square value for the surface EMG of the biceps brachii and exerted force within 50 ms before TMS was also calculated (RMS/F)., Results: In two subjects, no significant changes in MVC and muscle soreness were seen after ECC so that their data was excluded from further analysis. Control MVC and muscle soreness was significantly decreased and increased, respectively, 2 and 4 d after ECC compared with that before ECC (P < 0.001). During the fatigue test, VA, which was determined by a phasic increase in the twitch force after TMS, significantly decreased 2 and 4 d after ECC compared with that beforehand (P < 0.01). In addition, the RMS/F was significantly increased 2 and 4 d after ECC (P < 0.001). Although the degree of facilitation of the MEP was significantly increased (P < 0.05), the length of EMG silencing was less affected by ECC., Conclusions: Muscle damage and/or muscle soreness induced by repetitive eccentric exercise with maximal effort may be a strong modifier of central and peripheral fatigue during sustained MVC.