Pulmonary dead space (VD) is the sum of the airways that do not participate in gas exchange. In pulmonary diseases gas exchange and ventilation abnormalities result from a reduction in the total surface area of the blood gas barrier. This results in high VD/VT and poor ventilatory efficiency. Dead space loading (DSL) is a useful tool for studying VD/VT abnormalities in isolation of heterogeneous disease processes. While it is clear DSL worsens exercise tolerance, the ventilatory abnormalities have not been confirmed to directly affect locomotor fatigue. The evidence overwhelmingly points to a consistent increase in the work of breathing and a decrease in exercise tolerance with DSL. How and if these are connected remains uncertain. OBJECTIVE Measure the effect of DSL on locomotor fatigue dynamics, ventilatory variables, leg fatigue, and exercise tolerance. METHODS Twenty-six participants (26yr, 172cm, 72kg, 12 women, 14 men) completed constant, supra- critical power bouts to intolerance with and without DSL (600mL) in a counterbalanced order. We measured maximal locomotor power throughout the test with 5 s interleaved maximal isokinetic sprints. RESULTS There was no difference in locomotor fatigue dynamics between the control and DSL (F[1, 50]=0.06, p>0.814; CIDiff-78, 99 W). Exercise tolerance was worsened with DSL by 30(66) s (t=2.32, df=25, p<0.03, η2=0.18, CIDiff -57, -3 s). V̇ E at ‘isotime’ was greater with DSL by 6.8(14.5) L/min (t=2.38, df=25, p<0.026, η2=0.19, CIDiff 0.92, 12.68 L/min). V̇ O2 at ‘isotime’ was not different in control vs DSL (t = 0.57, df = 25, p > 0.574, η2 = 0.013). There was no difference in perceived leg fatigue (p>0.24) or dyspnea (p>0.08). CONCLUSIONS DSL shortened exercise tolerance and resulted in greater ventilation at ‘isotime’. However, DSL did not affect locomotor fatigue dynamics. This suggests the poor exercise tolerance with DSL results from excessive work of ventilation and not necessarily from a direct negative impact on locomotor power.