This experiment examined the effect of a moderate dose of caffeine on quadriceps muscle pain during a bout of high-intensity cycling in low- versus high-caffeine-consuming males. College-age men who were low (≤100 mg/day; n = 12) or high (≥400 mg/day; n = 13) habitual caffeine consumers ingested caffeine (5 mg/kg body weight) or a placebo in a counterbalanced order and 1 hr later completed 30 min of cycle ergometry at 75–77% of peak oxygen consumption. Perceptions of quadriceps muscle pain, as well as oxygen consumption, heart rate, and work rate, were recorded during both bouts of exercise. Caffeine ingestion resulted in a statistically significant and moderate reduction in quadriceps muscle-pain-intensity ratings during the 30-min bout of high-intensity cycle ergometry compared with placebo ingestion in both low (d = −0.42) and high (d = −0.55) caffeine consumers. The results suggest that caffeine ingestion is associated with a moderate hypoalgesic effect during high-intensity cycling in college-age men who are low or high habitual caffeine consumers, but future work should consider better defining and differentiating pain and effort when examining the effects of caffeine during acute exercise.