The metabolic stress induced by blood flow restriction (BFR) during resistance training (RT) might maximize muscle growth. However, it is currently unknown whether metabolic stress are associated with muscle hypertrophy after RT protocols with high- or low load. Therefore, the aim of the study was to compare the effect of high load RT (HL-RT), high load BFR (HL-BFR), and low load BFR (LL-BFR) on deoxyhemoglobin concentration [HHb] (proxy marker of metabolic stress), muscle cross-sectional area (CSA), activation, strength, architecture and edema before (T1), after 5 (T2), and 10 weeks (T3) of training with these protocols. Additionally, we analyzed the occurrence of association between muscle deoxygenation and muscle hypertrophy. Thirty young men were selected and each of participants' legs was allocated to one of the three experimental protocols in a randomized and balanced way according to quartiles of the baseline CSA and leg extension 1-RM values of the dominant leg. The dynamic maximum strength was measured by 1-RM test and vastus lateralis (VL) muscle cross-sectional area CSA echo intensity (CSAecho) and pennation angle (PA) were performed through ultrasound images. The measurement of muscle activation by surface electromyography (EMG) and [HHb] through near-infrared spectroscopy (NIRS) of VL were performed during the training session with relative load obtained after the 1-RM, before (T1), after 5 (T2), and 10 weeks (T3) training. The training total volume (TTV) was greater for HL-RT and HL-BFR compared to LL-BFR. There was no difference in 1-RM, CSA, CSAecho, CSAecho/CSA, and PA increases between protocols. Regarding the magnitude of the EMG, the HL-RT and HL-BFR groups showed higher values than and LL-BFR. On the other hand, [HHb] was higher for HL-BFR and LL-BFR. In conclusion, our results suggest that the addition of BFR to exercise contributes to neuromuscular adaptations only when RT is performed with low-load. Furthermore, we found a significant association between the changes in [HHb] (i.e., metabolic stress) and increases in muscle CSA from T2 to T3 only for the LL-BFR, when muscle edema was attenuated.