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This investigation examined the ergogenic effect of short-term oral N-acetylcysteine (NAC) supplementation and the associated changes in redox balance and inflammation during intense training.A double-blind randomized placebo-controlled crossover design was used to assess 9 d of oral NAC supplementation (1200 mg·d−1) in 10 well-trained triathletes. For each supplement trial (NAC and placebo), baseline venous blood and urine samples were taken, and a presupplementation cycle ergometer race simulation was performed. After the loading period, further samples were collected preexercise, postexercise, and 2 and 24 h after the postsupplementation cycle ergometer race simulation. Changes in total antioxidant capacity, ferric reducing ability of plasma, reduced glutathione, oxidized glutathione, thiobarbituric acid-reactive substances, interleukin 6, xanthine oxidase, hypoxanthine, monocyte chemotactic protein 1, nuclear factor κB, and urinary 15-isoprostane F2t concentration were assessed. The experimental procedure was repeated with the remaining supplement after a 3-wk washout. Eight participants completed both supplementation trials.NAC improved sprint performance during the cycle ergometer race simulation (P < 0.001, ηp2 = 0.03). Supplementation with NAC also augmented postexercise plasma total antioxidant capacity (P = 0.005, ηp2 = 0.19), reduced exercise-induced oxidative damage (plasma thiobarbituric acid-reactive substances, P = 0.002, ηp2 = 0.22; urinary 15-isoprostane F2t concentration, P = 0.010, ηp2 = 0.431), attenuated inflammation (plasma interleukin 6, P = 0.002, ηp2 = 0.22; monocyte chemotactic protein 1, P = 0.012, ηp2 = 0.17), and increased postexercise nuclear factor κB activity (P < 0.001, ηp2 = 0.21).Oral NAC supplementation improved cycling performance via an improved redox balance and promoted adaptive processes in well-trained athletes undergoing strenuous physical training.