High-intensity exercise [90% of maximal O₂ uptake (VO_2max)] sustained to the limit of tolerance elicits expiratory muscle fatigue (EMF). We asked whether prior EMF affects subsequent exercise tolerance. Eight male subjects (mean±SD VO_2max=53.5±5.2 ml·kg^-1·min^-1) cycled at 90% of peak power output (W_peak) to the limit of tolerance with (EMF-EX) and without (CON-EX) prior induction of EMF, and for a time equal to that achieved in EMF-EX but without prior induction of EMF (ISO-EX). To induce EMF, subjects breathed against an expiratory flow resistor until task failure (15 breaths·min^-1, 0.7 expiratory duty cycle, 40% of maximal expiratory gastric pressure). Abdominal and quadriceps muscle fatigue were assessed by measuring the reduction relative to prior baseline values in magnetically evoked gastric twitch pressure (P_ga,tw) and quadriceps twitch force (Q_tw), respectively. The reduction in P_ga,tw was not different after resistive breathing vs. after CON-EX (-27±5 vs. -26±6%,P=0.127). Exercise-time was reduced by 33±10% in EMF-EX vs. CON-EX (6.85±2.88 vs. 9.90±2.94 min, P<0.001). Exercise-induced abdominal and quadriceps muscle fatigue were greater after EMF-EX vs. ISO-EX (P_ga,tw -28±9 vs. -12±5%, P=0.001; Q_tw -28±7 vs. -14±6%, P=0.015). Perceptual ratings of dyspnea and leg discomfort (Borg CR10) were higher at 1 and 3 min, and at end exercise during EMF-EX vs. ISO-EX (P<0.05). Percent changes in limb fatigue and leg discomfort (EMF-EX vs. ISO-EX) correlated significantly with the change in exercise-time. We propose that EMF impaired subsequent exercise tolerance primarily through an increased severity of limb locomotor muscle fatigue and a heightened perception of leg discomfort.