Background Oxidative stress has been defined as a disturbance in the equilibrium status of pro-oxidant and antioxidant systems in favour of pro-oxidation. The elevated metabolic rate associated with exercise leads to increased mitochondrial oxygen consumption in tissues, free radical generation, metabolite oxidation and antioxidant depletion. Objective The aim of the present work was to examine the association of iron depletion and acute phase response with oxidative stress in female athletes. Setting and participants Based on serum ferritin values (cut-off 22 μg/L), 54 elite female volleyball athletes were divided into two groups: with iron depletion and with normal iron stores. Samples were taken from athletes who were members of the top two senior women volleyball teams in Serbia during the 2007/2008 competition season. Interventions The following parameters were measured: ferritin, C-reactive protein, interleukin-6, oxidative stress parameters (reactive oxygen metabolites – ROMs and lipid hydroperoxides – LOOH) and antioxidative defence parameters (biological antioxidative potential – BAP and superoxide-dismutase). Results A general linear model indicated significant differences between athletes (Wilks's λ=0.698, F=5.092, p=0.002) in reactive oxygen metabolites (278±57 vs 333±56; p=0.001) which were significantly higher in athletes with iron depletion and biological antioxidative potential (2547±257 vs 2366±297; p=0.026) which was significantly lower in this group. Besides iron depletion, multivariate analysis of covariance revealed C-reactive protein (pConclusions Oxidative stress that occurs during exercise is related to acute phase response and iron depletion plays a significant role in processes that lead to free radical generation in professional athletes. Athletes with ferritin values below 22 μg/L had a decreased antioxidatve defence and were more susceptible to oxidative stress compared to those with adequate iron status.