Purpose: In theory, a slow oxygen uptake ( V˙O2 ) kinetics leads to a greater accumulation of anaerobic by-products, which can, in turn, induce more neuromuscular fatigue. However, the existence of this relationship has never been tested. Methods: After two sessions to measure peak V˙O2 , peak power output (POpeak), and V˙O2 kinetics responses in the unfatigued state (τ V˙O2 MOD), 10 healthy young adults performed a 6-min cycling bout at 80% POpeak (INT6-min). V˙O2 kinetics responses were also measured during INT6-min. Neuromuscular fatigue was measured isometrically pre- and post-INT6-min (immediately post- and 15-s post-INT6-min) with an innovative cycle ergometer. Results: Maximal voluntary contraction (MVC) force, high-frequency doublet amplitude, and the ratio of low- to high-frequency doublet amplitudes decreased by 34 ± 7, 43 ± 11, and 31 ± 13%, respectively (all P < 0.01). A significant Spearman’s rank correlation was observed between the change in low-frequency doublet force (ΔDb10) immediately after INT6-min and both τ V˙O2 MOD and τ V˙O2 INT6-min (ρ = −0.68 and ρ = −0.67, both P < 0.05). When considering the largest responses from the two neuromuscular evaluations post-INT6-min, significant correlations were also found between τ V˙O2 MOD and ΔDb10 (ρ = −0.74; P < 0.05) and between τ V˙O2 INT6-min and both ΔDb10 and low-frequency fatigue (ρ = −0.70 and ρ = −0.66; both P < 0.05). Conclusion: The present results suggest that subjects with slow V˙O2 kinetics experience more peripheral fatigue, in particular more excitation–contraction coupling failure, likely due to a greater accumulation of protons and/or inorganic phosphates.