We investigated the influence of short‐ and long‐interval cycling exercise with blood flow restriction (BFR) on neuromuscular fatigue, shear stress and muscle oxygenation, potent stimuli to BFR‐training adaptations. During separate sessions, eight individuals performed short‐ (24 × 60 s/30 s; SI) or long‐interval (12 × 120 s/60 s; LI) trials on a cycle ergometer, matched for total work. One leg exercised with (BFR‐leg) and the other without (CTRL‐leg) BFR. Quadriceps fatigue was quantified using pre‐ to post‐interval changes in maximal voluntary contraction (MVC), potentiated twitch force (QT) and voluntary activation (VA). Shear rate was measured by Doppler ultrasound at cuff release post‐intervals. Vastus lateralis tissue oxygenation was measured by near‐infrared spectroscopy during exercise. Following the initial interval, significant (P textless 0.05) declines in MVC and QT were found in both SI and LI, which were more pronounced in the BFR‐leg, and accounted for approximately two‐thirds of the total reduction at exercise termination. In the BFR‐leg, reductions in MVC (–28 ± 15%), QT (–42 ± 17%), and VA (–15 ± 17%) were maximal at exercise termination and persisted up to 8 min post‐exercise. Exercise‐induced muscle deoxygenation was greater (P textless 0.001) in the BFR‐leg than CTRL‐leg and perceived pain was more in LI than SI (P textless 0.014). Cuff release triggered a significant (P textless 0.001) shear rate increase which was consistent across trials. Exercise‐induced neuromuscular fatigue in the BFR‐leg exceeded that in the CTRL‐leg and was predominantly of peripheral origin. BFR also resulted in diminished muscle oxygenation and elevated shear stress. Finally, short‐interval trials resulted in comparable neuromuscular and haemodynamic responses with reduced perceived pain compared to long‐intervals.