Abstract: Comstock, BA, Thomas, GA, Dunn-Lewis, C, Volek, JS, Szivak, TK, Hooper, DR, Kupchak, BR, Flanagan, SD, Denegar, CR, and Kraemer, WJ. Effects of acute resistance exercise on muscle damage and perceptual measures between men who are lean and obese. J Strength Cond Res 27(12): 3488–3494, 2013—The purpose of this investigation was to assess indices of muscle damage and psychological stress between young, untrained, lean, and obese men. Using a between-subject design, 19 young men (9 lean men [age, 20.1 ± 2.1 years; body mass, 71.7 ± 5.8 kg; height, 177.8 ± 8.7 cm; body fat (BF), 14.7 ± 3.5%], 5 World Health Organization [WHO] class 1 obese men [age, 21.6 ± 2.5 years; body mass, 97.8 ± 8.6 kg; height, 176.3 ± 3.7 cm; BF, 34.7 ± 3.0%], and 5 WHO class 2 or 3 men [age, 20.0 ± 1.4 years; body mass, 120.8 ± 10.5 kg; height, 177.7 ± 5.2 cm; BF, 40.5 ± 5.8%]) volunteered and completed an acute resistance exercise (RE) protocol (6 exercises performed for 3 sets of 10 repetitions at an intensity of 85–95% of a 10 repetition maximum). Plasma myoglobin and serum creatine kinase were obtained before and immediately after exercise, and in recovery (at +110 minutes and +24 hours). Perceptual measures including rating of perceived exertion, pain and soreness, fatigue, and general soreness were assessed at different time points (during exercise for rating of perceived exertion, and for the fatigue and soreness measures before, immediately after, and at 24 hours of recovery from exercise). The primary findings of this investigation were that lean and obese, sedentary, young men do not significantly differ from each other in terms of indirect, humoral measures of muscle damage, or perceptual scales in response to a moderate-intensity acute RE bout, despite using significantly more exercise volume relative to fat mass (FM). We conclude that excess FM during daily activities of life provides a protective effect for muscle damage. When strength training individuals who are obese, practitioners should be aware of how excess FM affects muscle damage and total volume. But these considerations do not preclude individuals who are obese from using well-designed RE workouts which use free-weight, multijoint movements that stimulate all of the major muscle groups.