Purpose:This study investigated the supraspinal processes of fatigue of the quadriceps muscle in response to repeated cycling sprints.Methods:Twelve active individuals performed 10 × 6-s "all-out" sprints on a cycle ergometer (recovery = 30 s), followed 6 min later by 5 × 6-s sprints (recovery = 30 s). Transcranial magnetic and electrical femoral nerve stimulations during brief (5-s) and sustained (30-s) isometric contractions of the knee extensors were performed before and 3 min post-exercise.Results:Maximal strength of the knee extensors decreased during brief and sustained contractions (∼11% and 9%, respectively; P<0.001). Peripheral and cortical voluntary activation, motor evoked potential amplitude and silent period duration responses measured during briefs contractions were unaltered (P>0.05). While cortical voluntary activation declined (P<0.01) during the sustained maximal contraction in both test sessions, larger reductions occurred (P<0.05) after exercise. Lastly, resting twitch amplitude in response to both femoral nerve and cortical stimulations was largely (> 40%) reduced (P<0.001) following exercise.Conclusion:The capacity of the motor cortex to optimally drive the knee extensors following a repeated-sprint test was shown in sustained, but not brief, maximal isometric contractions. Additionally, peripheral factors were largely involved in the exercise-induced impairment in neuromuscular function, while corticospinal excitability was well-preserved.