This study investigated the occurrence of core muscle fatigue during high-intensity running exercise and its limitation to exercise performance. A secondary aim was to investigate whether respiratory muscle work performed during intense running periods, would contribute to core muscle fatigue. Nine male recreational runners were recruited for two reasons; (1) to perform a continuous treadmill run at 85% VO₂max with and without core muscle fatigue in the CR_F and CR trials, respectively; and (2) to mimic the treadmill run-induced respiratory response recorded in the CR trial while subjects were free of whole-body exercise (Mimic trial). The changes in global core muscle function with fatigue in this study were evaluated by performing a sport-specific endurance plank test (SEPT), and the associated influence on running performance was examined by comparing the time to exhaustion during the treadmill run between the CR and CR_F trials. Subsequent to the treadmill run in the CR trial, SEPT (255.7 ± 85.3 vs 177.3 ± 80.6 s) was reduced from baseline in all runners. The reduction correlated (r = 0.67) with the concomitant decline in inspiratory muscle function revealed by maximal inspiratory mouth pressure (PI_max: 151.3 ± 18.2 vs 133.3 ± 17.2 cmH₂O, p < 0.05). In the Mimic trial, similar results in SEPT (212.3 ± 90.2 s), PI_max (129.0 ± 26.7 cmH₂O), and correlation (r = 0.77, p < 0.05) were observed following voluntary hyperpneic activity. With the preceded fatigued core muscle workout in the CR_F trial, the running capacity was impaired significantly (10.7 ± 4.5 vs 6.5 ± 2.0 min, p < 0.05). The impairment was correlated (r=0.72) to the SEPT reduction resulting from the workout. The results suggest that a high-intensity maximum run may induce core muscle fatigue in runners. The core muscle fatigue, which may be partly attributed to the corresponding respiratory work, may limit their running endurance. Inspiratory muscle function appears to be essential for core stabilization during the intense running.