Polyphenols are of increasing interest to consumers and food manufacturers for several reasons. Commonly referred to as antioxidants (they are the most abundant antioxidants in our diets), they may prevent various oxidative stress-related diseases, such as cancer, cardiovascular disease, inflammation and others. Physical activity is known to induce oxidative stress in individuals after intensive exercise. In this study, the effect of the flavonoid contents (which are the most abundant polyphenols) was investigated, as the only antioxidant in a replacement drink designed for sportsmen on various oxidative stress biomarkers after two identical trials of sub-maximal aerobic exercise, in a group of 30 sportsmen. In one of the trials, the cyclists consumed the antioxidant supplement (with 2.3g polyphenols/trial), and in another they consumed a placebo. Blood samples were collected both at rest and after exercise immediately and 45 minutes (min) later, for measurements of plasmatic indices of oxidative stress: lipid oxidation (TBARS), total antioxidant status (TAS); protein oxidation (carbonyl groups, CO) and the lactate dehydrogenase (LDH) and creatine kinase (CK) enzymes for each trial. All values were adjusted for changes in plasma volume. No changes were detected in plasma TAS and LDH after exercise or after the polyphenolic supplement. CK and TBARS increased after exercise in both tests. However, in response to strenuous exercise, the polyphenol-supplemented test showed a smaller increase in plasma TBARS and CK than the placebo test. CO increased by 12% in response to the placebo test, whereas it decreased by 23% in the polyphenol-supplement test. This may indicate that the antioxidant supplement offered protection against exercise-induced oxidative stress.