Purpose Low-load blood-flow resistance training (LLBFRT) is increasingly used as an alternative to high-load resistance training (HLRT) to improve muscle strength and endurance while reducing mechanical stress on tissues. However, the acute responses associated with LLBFRT during sport climbing-specific exercises remain unknown. The aims of the study were to describe muscle oxygenation, fatigue and perceptual responses to climbing-specific finger flexors exercise in LLBFRT and compare such responses to HLRT. Methods Fifteen advanced to elite climbers took part in three visits: a familiarization session and two randomized finger-flexors training sessions in either HLRT (3 sets of 10–12 repetitions, ~70% maximal voluntary contraction, MVC) or LLBFRT (3 sets of 14–20 repetitions, ~40%MVC with cuff set at 60% of limb occlusion pressure). Finger flexors muscle oxygenation was assessed using near-infrared spectroscopy. Force–time integral (FTI) quantified mechanical load under both modalities. Muscle fatigue was quantified as force loss from pre- to 1-min, 5-min and 15-min post-exercise. Perceived discomfort, effort, and finger pain were assessed after each set. Results LLBFRT led to greater muscle deoxyhemoglobin values (+20 ± 25%, p = 0.005, d = 0.9) during exercise. Despite lower FTI (−7 ± 10%, p = 0.028), muscle fatigue was greater in LLBFRT than HLRT 1-min post-exercise (−24.8 ± 7.9 vs −18.6 ± 7.4%MVC, p = 0.016) but not 5-min and 15-min post-exercise. LLBFRT caused greater discomfort during inter-set recovery but lower finger pain during exercise. Conclusion Climbing-specific LLBFRT induced a transient increase in finger flexors muscle deoxygenation and fatigue likely due to elevated metabolic stress and venous blood pooling, while reducing mechanical load and thus potentially lowering injury risk.