ABSTRACTThis paper aimed to examine the acute effect of low‐load (LL) exercise with blood‐flow restriction (LL‐BFR) on microvascular oxygenation and muscle excitability of the vastus medialis (VM) and vastus lateralis (VL) muscles during a single bout of unilateral knee extension exercise performed to task failure. Seventeen healthy recreationally resistance‐trained males were enrolled in a within‐group randomized cross‐over study design. Participants performed one set of unilateral knee extensions at 20% of one‐repetition maximum (1RM) to task failure, using a LL‐BFR or LL free‐flow (LL‐FF) protocol in a randomized order on separate days. Changes in microvascular oxygenation and muscle excitability in VL and VM were assessed using near‐infrared spectroscopy (NIRS) and surface electromyography (sEMG), respectively. Pain measures were collected using the visual analog scale (VAS) before and following set completion. Within‐ and between‐ protocol comparisons were performed at multiple time points of set completion for each muscle. During LL‐BFR, participants performed 43% fewer repetitions and reported feeling more pain compared to LL‐FF (p<0.05). Normalized to time to task failure, LL‐BFR and LL‐FF generally demonstrated similar progression in microvascular oxygenation and muscle excitability during exercise to task failure. The present results demonstrate that LL‐BFR accelerates time to task failure, compared with LL‐FF, resulting in a lower dose of mechanical work to elicit similar levels of oxygenation, blood‐pooling, and muscle excitability. LL‐BFR may be preferable to LL‐FF in clinical settings where high workloads are contraindicated, although increased pain experienced during BFR may limit its application.Highlights Compared to free flow (FF), neuromuscular fatigue mechanisms are accelerated during blood flow restricted (BFR) training. This can be observed as changes in microvascular oxygenation and muscle excitability occurring at a ∼43% faster mean rate during BFR compared to FF. BFR exercise seems to elicit the same level of neuromuscular fatigue as FF training within a shorter timeframe. This reduces total joint load and may be especially helpful in cases where high training volumes may be contraindicated (e.g. recovering from a sports injury or orthopedic surgery).