This study investigated the changes in muscular activity and tissue oxygenation while lifting and lowering a load of 20, 40, 60 or 80 % of one repetition maximum (1RM) with elbow flexor muscles until failure. The surface electromyogram (EMG) was recorded in biceps brachii (BB), brachioradialis (BRD) and triceps brachii (TB). For BB, a tissue oxygenation index (TOI) and a normalized total hemoglobin index (nTHI) were recorded by near-infrared spectroscopy. The number of repetitions decreased with the increase in load (P < 0.001), and the four loading conditions induced a decrease in MVC force immediately after failure (P < 0.001). The average of rectified EMG amplitude (aEMG) of elbow flexors increased for all loads during muscle shortening (SHO) and lengthening (LEN) phases of the movement (P < 0.05), except for the 80 % load during LEN phase. At failure, the aEMG was greater during the SHO than the LEN phase (P < 0.05), except for the 20 % load. TOI decreased for all loads and phases (P < 0.05) but less (P < 0.01) for the 20 % than 60 and 80 % loads (P < 0.01), and for LEN compared with SHO phase. At failure, TOI was negatively associated with aEMG during the SHO (r(2) = 0.99) and LEN (r(2) = 0.82) phases, while TOI and aEMG were positively associated with load magnitude (r(2) > 0.90) in both movement phases. This study emphasizes the influence of load magnitude and movement phase (SHO and LEN) on neuromuscular and oxydative adjustments during movements that involve lifting and lowering a load until failure.