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The purpose of the present study was to evaluate the ‘normobaric oxygen paradox’ theory by investigating the effect of a 2-h normobaric O2 exposure on the concentration of plasma erythropoietin (EPO).Ten healthy males were studied twice in a single-blinded counterbalanced crossover study protocol. On one occasion they breathed air (NOR) and on the other 100% normobaric O2 (HYPER). Blood samples were collected Pre, Mid and Post exposure; and thereafter, 3, 5, 8, 24, 32, 48, 72 and 96 h, and 1 and 2 weeks after the exposure to determine EPO concentration.The concentration of plasma erythropoietin increased markedly 8 and 32 h after the NOR exposure (approx. 58% and approx. 52%, respectively, P ≤ 0.05) as a consequence of its natural diurnal variation. Conversely, the O2 breathing was followed by approx. 36% decrement of EPO 3 h after the exposure (P ≤ 0.05). Moreover, EPO concentration was significantly lower in HYPER than in the NOR condition 3, 5 and 8 h after the breathing intervention (P ≤ 0.05).In contrast to the ‘normobaric oxygen paradox’ theory, the present results indicate that a short period of normobaric O2 breathing does not increase the EPO concentration in aerobically fit healthy males. Increased O2 tension suppresses the EPO concentration 3 and 5 h after the exposure; thereafter EPO seems to change in a manner consistent with natural diurnal variation.