Resistance training plays a key role in enhancing muscular performance; however, the effects of different combinations of loading intensity and velocity loss (VL) thresholds on muscle oxygen saturation (SmO₂) dynamics during exercise remain insufficiently understood. This study aimed to investigate the influence of intensity (60% vs. 80% one-repetition maximum [1RM]) and VL (20% vs. 40%) on SmO₂ responses during the back squat exercise. Eighteen resistance-trained males (age: 20.06 ± 1.63 years; height: 176.78 ± 6.45 cm; body mass: 70.26 ± 9.56 kg) performed four back squat protocols - 60%1RM-VL20% (60-20), 60%1RM-VL40% (60-40), 80%1RM-VL20% (80-20), and 80%1RM-VL40% (80-40) - using a repeated-measures, counterbalanced design. Each protocol comprised three sets with 5-minute inter-set rest periods. SmO₂ of the vastus lateralis was continuously monitored to determine changes in its magnitude and slope during exercise and recovery phases. Results revealed no significant differences were observed in the magnitude of SmO₂ decline across conditions, with values ranging from 47.28% to 57.67% across all sets (p > .05). The SmO₂ decline slope was significantly steeper (more negative) in the 80-20 condition (-1.71 to -2.04 %·s^-1) compared to both 60-20 (-0.80 to -1.13 %·s^-1) and 60-40 (-0.53 to -1.00 %·s^-1) across all sets (p < .001). No significant differences were observed in SmO₂ recovery slope during rest (range: 0.36-0.61 %·s^-1; p > .05). The present study demonstrated that combining 60% 1RM with a 40% VL% threshold elicited the slowest SmO₂ decline rate, potentially delaying fatigue onset and allowing greater repetition volume. Although both training intensity and velocity loss thresholds influenced muscle oxygenation dynamics, the rate of SmO₂ desaturation was particularly sensitive to changes in VL% thresholds under the 80% 1RM. These findings underscore the importance of integrating training intensity, VL% magnitude, and oxygenation dynamics when designing individualized resistance training protocols.

• The magnitude of muscle oxygen saturation decline during the back squat exercise is not influenced by training intensity or velocity loss magnitude.

• The 60%1RM-VL40% condition exhibited the slowest rate of SmO decline, potentially delaying fatigue and allowing more repetitions, thereby increasing total contraction time without inducing abrupt physiological stress.

• Both training intensity and velocity loss settings influence muscle oxygenation dynamics, with the rate of muscle oxygen desaturation being particularly sensitive to changes in velocity loss thresholds under 80% 1RM conditions.