The aim was evaluating the effects of hypoxia/reoxygenation repetitive episodes during 5 days of apnea diving (3-day training/2-day competition) on peripheral blood mononuclear cells (PBMCs) antioxidant defenses, oxidative damage, and plasma xanthine oxidase activity. Blood samples, from seven professional apnea divers, were taken under basal conditions the previous morning to the first training session (pre-diving basal), 4 h after ending the competition (4 h post-diving) and the following morning (15 h after last dive) in basal conditions (post-diving basal). Glucose levels significantly decreased whereas triglycerides increased at 4 h post-diving, both returning to basal values at post-diving basal. Glutathione reductase and catalase activity significantly increased after 4 h post-diving remaining elevated at post-diving basal. Glutathione peroxidase and superoxide dismutase activities and catalase protein levels progressively increased after diving with significant differences respect to initial values at post-diving basal. No significant differences were observed in circulating PBMCs and oxidative damage markers. Plasma xanthine oxidase activity and nitrite levels, but not the inducible nitric oxide synthetase, significantly increased 4 h post-diving, returning to the basal values after 15 h. In conclusion, chronic and repetitive episodes of diving apnea during five consecutive days increased plasma xanthine oxidase activity and nitric oxide production which could enhance the signalling role of reactive oxygen and nitrogen species for PBMCs antioxidant adaptation against hypoxia/reoxygenation.