Fatigue induced via a maximal isometric contraction of a single-limb muscle group can evoke a “cross-over” of fatigue that reduces voluntary muscle activation and maximum isometric force in the rested contralateral homologous muscle group. We asked whether a cross-over of fatigue also occurs when fatigue is induced via high-intensity endurance exercise involving a substantial muscle mass. Specifically, we used high-intensity single-leg cycling to induce fatigue and evaluated associated effects on maximum cycling power (Pmax) in the fatigued ipsilateral leg (FATleg) as well as the rested contralateral leg (RESTleg). On separate days, 12 trained cyclists performed right leg Pmax trials before and again 30s, 3, 5, and 10min after a cycling time trial (TT, 10min) performed either with their right or left leg. Fatigue was estimated by comparing exercise-induced changes in Pmax and maximum handgrip isometric force (Fmax). Mean power produced during the right and left leg TT’s did not differ (203±8 vs. 199±8W). Compared to pre-TT, FATleg Pmax was reduced by 22±3% at 30s post-TT and remained reduced by 9±2% at 5min post-TT (both P<0.05). Despite considerable power loss in the FATleg, post-TT RESTleg Pmax (596–603W) did not differ from pre-TT values (596±35W). There were no alterations in handgrip Fmax (529–547N). Our data suggest that any potential cross-over of fatigue, if present at all, was not sufficient to measurably compromise RESTleg Pmax in trained cyclists. These results along with the lack of changes in handgrip Fmax indicate that impairments in maximal voluntary neuromuscular function were specific to working muscles.