The present research was designed to evaluate the adaptive responses to oxidative stress and inflammation in handball players subjected to well-controlled training intervals over one-year of competition. Seven blood samples were collected over the season of the study, approximately one a month. Plasma lipid peroxidation, nitrite, cytokines (IL-1β, IL-6, INFγ and TNFα), and the glutathione cycle in erythrocytes, were measured. Exercise intensity, measured with the Borg's scale, increased significantly up to the middle of the competition season, coinciding with maximal creatine kinase and lactate dehydrogenase values, and then decreased at the end of the study. The inflammatory markers including nitrite, IL-1β, IL-6, and, to a lesser extent INFγ, increased early in the training season, and remained elevated until the end of the study. TNFα, however, remained low during the season. The oxidative stress response included a transient increase of the glutathione disulphide/glutathione ratio and glutathione reductase activity at the beginning of the study, returning to basal values somewhat later. Glutathione peroxidase also increased at the end of the training season, and lipid peroxidation levels remained low during the athletic season. These results suggest that well-trained athletes were best adapted to the oxidative response, although the beneficial effects of some of the inflammatory cytokines on skeletal muscle myogenesis and repair cannot be ruled out.