Exercise-induced fatigue affects the motor control and the ability to generate a given force or power. Surface electroencephalography allows researchers to investigate movement-related cortical potentials (MRCP), which reflect preparatory brain activity 1.5 s before movement onset. Although the MRCP amplitude appears to increase after repetitive single-joint contractions, the effects of large-muscle group dynamic exercise on such pre-motor potential remain to be described. Sixteen volunteers exercised 30 min at 60% of the maximal aerobic power on a cycle ergometer, followed by a 10-km all-out time trial. Before and after each of these tasks, knee extensor neuromuscular function was investigated using maximal voluntary contractions (MVC) combined with electrical stimulations of the femoral nerve. MRCP was recorded during 60 knee extensions after each neuromuscular sequence. The exercise resulted in a significant decrease in the knee extensor MVC force after the 30-min exercise (-10 ± 8%) and the time trial (-21 ± 9%). The voluntary activation level (VAL; -6 ± 8 and -12 ± 10%), peak twitch (Pt; -21 ± 16 and -32 ± 17%), and paired stimuli (P100 Hz; -7 ± 11 and -12 ± 13%) were also significantly reduced after the 30-min exercise and the time trial. The first exercise was followed by a decrease in the MRCP, mainly above the mean activity measured at electrodes FC1-FC2, whereas the reduction observed after the time trial was related to the FC1-FC2 and C2 electrodes. After both exercises, the reduction in the late MRCP component above FC1-FC2 was significantly correlated with the reduction in P100 Hz (r = 0.61), and the reduction in the same component above C2 was significantly correlated with the reduction in VAL (r = 0.64). In conclusion, large-muscle group exercise induced a reduction in pre-motor potential, which was related to muscle alterations and resulted in the inability to produce a maximal voluntary contraction.