Production of reactive oxygen species (ROS) during muscle contractions is associated with muscle fatigue and damage in the short term and adaptive responses in the long term. When adaptation is inconsequential acute antioxidant supplementation may be able to attenuate muscle fatigue and damage to enhance performance. This study aimed to determine the effects of acute oral N-acetylcysteine (NAC) supplementation on Yo-Yo Intermittent Recovery Test Level 1 (YIRT-L1) performance after repeated bouts of damaging intermittent exercise. In a pair-matched design, 12 recreationally trained men engaged in 6 d of either NAC (n = 6) or placebo (n = 6) supplementation. After a treatment-loading day, participants completed 3 testing sessions, on alternating days, consisting of a preexercise isokinetic dynamometry (IKD) test, a damaging intermittent-exercise protocol, YIRT-L1, and a postexercise IKD test. Another IKD test was completed on the 2 intervening d. NAC treatment resulted in a significant preservation of YIRT-L1 performance (p ≤ .0005). IKD performance significantly deteriorated over time at all contraction speeds, and this deterioration was not influenced by treatment group. Plasma creatine kinase values increased significantly over time (p = .002) and were significantly greater in the NAC group than in the placebo group (p = .029). NAC induced mild gastrointestinal side effects. NAC supplementation may be a useful strategy to enhance performance during short-term competitive situations when adaption is inconsequential. Titration studies to elucidate a treatment dose that enhances performance without inducing side effects are now required.