Ventilatory equivalents for oxygen and carbon dioxide are physiological measures of breathing efficiency, and are known to be affected by the intensity and mode of exercise. We examined the effect of level running (gradient 0%) and muscle-damaging downhill running (−12%), matched for oxygen uptake, on the ventilatory equivalents for oxygen () and carbon dioxide (). Nine men (27 ± 9 years, 179 ± 7 cm, 75 ± 12 kg, : 52.0 ± 7.7 mL·kg−1·min−1) completed two 40-min running bouts (5 × 8-min with 2-min inter-bout rest), one level and one downhill. Running intensity was matched at 60% of maximal metabolic equivalent. Maximal isometric force of m.quadriceps femoris was measured before and after the running bouts. Data was analyzed with 2-way ANOVA or paired samples t-tests. Running speed (downhill: 13.5 ± 3.2, level: 9.6 ± 2.2 km·h−1) and isometric force deficits (downhill: 17.2 ± 7.6%, level: 2.0 ± 6.9%) were higher for downhill running. Running bouts for level and downhill gradients had , heart rates and respiratory exchange ratio values that were not different indicating matched intensity and metabolic demands. During downhill running, the , (downhill: 29.7 ± 3.3, level: 27.2 ± 1.6) and (downhill: 33.3 ± 2.7, level: 30.4 ± 1.9) were 7.1% and 8.3% higher (p < 0.05) than level running. In conclusion, breathing efficiency appears lower during downhill running (i.e., muscle-damaging exercise) compared to level running at a similar moderate intensity.