Individuals often need to maintain voluntary contractions during high intensity exercise in the presence of fatigue and pain. This investigation examined the effects of pre‐induced fatigue and concurrent rising pain (evoked by muscle ischaemia) in one leg on motor fatigability and corticospinal excitability/inhibition of the contralateral limb. Twelve healthy males undertook four experimental protocols including unilateral cycling to task failure at 80% of peak power output with: (i) the right‐leg (RL); (ii) the left‐leg (LL); (iii) RL immediately preceded by LL protocol (FAT‐RL); and (iv) RL when blood flow was occluded in the contralateral (left) leg (PAIN‐RL). Participants performed maximal and submaximal 5 s right‐leg knee extensions during which transcranial magnetic and femoral nerve electrical stimuli were delivered to elicit motor‐evoked and compound muscle action potentials, respectively. The pre‐induced fatigue reduced the right leg cycling time‐to‐task failure (mean ± SD; 332 ± 137 s) to a greater extent than concurrent pain (460 ± 158 s), compared to RL (580 ± 226 s) (P < 0.001). The maximum voluntary contraction force declined less following FAT‐RL (P < 0.019) and PAIN‐RL (P < 0.032) compared to RL. Voluntary activation declined and the corticospinal excitability recorded from knee extensors increased similarly after the three conditions (P < 0.05). However, the pre‐induced fatigue, but not concurrent pain, reduced corticospinal inhibition compared to RL (P < 0.05). These findings suggest that regardless of the origin and/or mechanisms modulating sensory afferent feedback during single‐leg cycling (e.g. pre‐induced fatigue vs. concurrent rising pain), the limit of exercise tolerance remains the same, suggesting that exercise will be terminated upon achievement of sensory tolerance limit.