Exercise-induced muscle damage (EIMD) is known to decrease muscle strength and power but its effect on endurance performance is unclear. Thirty moderately trained adult runners (24 men and six women) were randomly assigned to EIMD or control. The EIMD group jumped 100 times from a 35 cm bench, while controls did not perform any muscle-damaging exercise. Before and 48 h after treatment, subjects were tested on markers of EIMD, steady-state cardiorespiratory, metabolic and perceptual responses during a constant speed submaximal run; distance ran in 30 min on a treadmill. There were significant changes in muscle soreness, creatine kinase, and knee extensors strength (P<0.01). This EIMD significantly reduced self-paced time trial performance by 4% (P<0.01) because subjects reduced running speed (P=0.02), with no change in perceived exertion (P=0.31). No significant alterations in running economy and other physiological responses to submaximal running were found. However, there was a trend (P=0.08) for increased perceived exertion, which was correlated with decreased time trial performance (P<0.01). In conclusion, EIMD has a significant impact on endurance running performance in humans, and this effect seems to be mediated by alterations in the sense of effort.