To investigate the influence of pre-induced fatigue in one leg on neuromuscular performance and corticospinal responses of the contralateral homologous muscles, three experiments were conducted with different exercise protocols; A (n = 12): a 60 s rest vs. time-matched sustained left leg knee extension maximum voluntary contraction (MVC), B (n = 12): a 60 s rest vs. time-matched left leg MVC immediately followed by 60 s right leg MVC, and C (n = 9): a similar protocol to experiment B, but with blood flow occluded in the left leg while the right leg was performing the 60 s MVC. The neuromuscular assessment included 5 s knee extensions at 100%, 75%, and 50% of MVC. At each force level, transcranial magnetic and peripheral nerve stimuli were elicited to investigate the influence of different protocols on the right (tested) knee extensors’ maximal force output, voluntary activation, corticospinal excitability, and inhibition. The pre-induced fatigue in the left leg did not alter the performance nor the neuromuscular responses recorded from the right leg in the three experiments (all p > 0.3). However, enhanced corticospinal pathway excitability was evident in the tested knee extensors (p = 0.002). These results suggest that the pre-induced fatigue and muscle ischemia in one leg did not compromise the central and peripheral components of the neuromuscular function in the tested contralateral leg.