PURPOSE:This study examined whether lower-volume exercise-induced muscle damage (EIMD) performed 2 weeks before high-volume muscle-damaging exercise protects against its detrimental effect on running performance. METHODS:Sixteen male participants were randomly assigned to a lower-volume (five sets of ten squats, n = 8) or high-volume (ten sets of ten squats, n = 8) EIMD group and completed baseline measurements for muscle soreness, knee extensor torque, creatine kinase (CK), a 5-min fixed-intensity running bout and a 3-km running time-trial. Measurements were repeated 24 and 48 h after EIMD, and the running time-trial after 48 h. Two weeks later, both groups repeated the baseline measurements, ten sets of ten squats and the same follow-up testing (Bout 2). RESULTS:Data analysis revealed increases in muscle soreness and CK and decreases in knee extensor torque 24-48 h after the initial bouts of EIMD. Increases in oxygen uptake [Formula: see text], minute ventilation [Formula: see text] and rating of perceived exertion were observed during fixed-intensity running 24-48 h after EIMD Bout 1. Likewise, time increased and speed and [Formula: see text] decreased during a 3-km running time-trial 48 h after EIMD. Symptoms of EIMD, responses during fixed-intensity and running time-trial were attenuated in the days after the repeated bout of high-volume EIMD performed 2 weeks after the initial bout. CONCLUSIONS:This study demonstrates that the protective effect of lower-volume EIMD on subsequent high-volume EIMD is transferable to endurance running. Furthermore, time-trial performance was found to be preserved after a repeated bout of EIMD.