The purpose of this study was to examine the effect of low- vs. high-intensity resistance exercise on lipid peroxidation. In addition, the role of muscle oxygenation on plasma malondialdehyde (MDA) concentrations was explored. Eleven experienced resistance trained male athletes (age: 20.8 ± 1.3 years; weight: 96.2 ± 14.4 kg; height: 182.4 ± 7.3 cm) performed 4 sets of the squat exercise using either a low-intensity, high-volume (LI; 15 repetitions at 60% 1 repetition maximum [1RM]) or high-intensity, low-volume (HI; 4 repetitions at 90% 1RM load). Venous blood samples were obtained before the exercise (PRE), immediately following the exercise (IP), and 20 (20P) and 40 minutes (40P) postexercise. Continuous wave near-infrared spectroscopy was used to measure muscle deoxygenation in the vastus lateralis during exercise. Deoxygenated Hb/Mb change was used to determine reoxygenation rate during recovery. No difference in MDA concentrations was seen between LI and HI at any time. Significant correlations were observed between plasma MDA concentrations at IP and the half-time recovery (T1/2 recovery) of muscle reoxygenation (r = 0.45) and between T1/2 recovery and the area under the curve for MDA concentrations (r = 0.44). Results suggest that increases in MDA occur independently of exercise intensity, but tissue acidosis may have a larger influence on MDA formation.