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Aim: We aimed to investigate the inter‐individual variability in redox and physiological responses of antioxidant‐deficient subjects after antioxidant supplementation. Methods: Two hundred individuals were sorted by plasma vitamin C levels. A low vitamin C group (n = 22) and a control group (n = 22) were compared in terms of oxidative stress and performance. Subsequently, the low vitamin C group received for 30 days vitamin C (1 g) or placebo, in randomized, double‐blind, crossover fashion, and the effects were examined through a mixed‐effects model, while individual responses were calculated. Results: The low vitamin C group exhibited lower vitamin C (−25 μmol/L; 95%CI[−31.7, −18.3]; p < 0.001), higher F2‐isoprostanes (+17.1 pg/mL; 95%CI[6.5, 27.7]; p = 0.002), impaired VO2max (−8.2 mL/kg/min; 95%CI[−12.8, −3.6]; p < 0.001) and lower isometric peak torque (−41.5 Nm; 95%CI[−61.8, −21.2]; p < 0.001) compared to the control group. Regarding antioxidant supplementation, a significant treatment effect was found in vitamin C (+11.6 μmol/L; 95%CI[6.8, 17.1], p < 0.001), F2‐isoprostanes (−13.7 pg/mL; 95%CI[−18.9, −8.4], p < 0.001), VO2max (+5.4 mL/kg/min; 95%CI[2.7, 8.2], p = 0.001) and isometric peak torque (+18.7; 95%CI[11.8, 25.7 Nm], p < 0.001). The standard deviation for individual responses (SDir) was greater than the smallest worthwhile change (SWC) for all variables indicating meaningful inter‐individual variability. When a minimal clinically important difference (MCID) was set, inter‐individual variability remained for VO2max, but not for isometric peak torque. Conclusion: The proportion of response was generally high after supplementation (82.9%–95.3%); however, a few participants did not benefit from the treatment. This underlines the potential need for personalized nutritional interventions in an exercise physiology context. [ABSTRACT FROM AUTHOR]