OBJECTIVE This study examined the effects of exercise-induced muscle damage (EIMD) on the physiological and perceptual responses to 30 minutes of submaximal cycling at 60% of oxygen consumption (VO2 peak). METHODS Ten participants completed two 30-minute bouts of cycling, one before and one 48 hours after performance of strenuous (24 contractions with 120% of concentric 1-repeition maximum) eccentric exercise. RESULTS Eccentric exercise resulted in a significant delayed-onset muscle pain (1.6±1.6 mm to 44.8±20 mm on a 100-mm visual analog scale; P<0.001) and a 15% (P<0.001) reduction in maximal strength 48 hours after exercise. Ratings of quadriceps muscle pain (1.99±0.42 vs. 3.30±0.56; P=0.003) and perceived exertion (RPE; 13.0±0.30 vs. 13.8±0.61; P=0.02) were elevated during cycling after EIMD at identical work rates. No changes were observed in VO2 (29.6±4.6 vs. 30.2±4.4 mL/kg/min; P=0.41), heart rate (154±15 vs. 155±9 beats/min; P=0.58), and ventilation (57.2±12.1 vs. 59.8±12.7 L/min; P=0.13) during exercise after EIMD. The mean change in RPE was significantly correlated (r=0.56; P<0.01) with the change in muscle pain during cycling and delayed-onset pain during resistance exercise (r=0.86; P<0.01), but did not correlate with changes in VO2, heart rate, ventilation, and maximal strength. CONCLUSIONS These findings indicate the elevations in RPE after EIMD are likely a consequence of the EIMD with the most likely explanation being an increase in localized pain before and during cycling exercise.