The gills and mantle are the first tissues exposed to altered oxidative conditions during dissolved Fe uptake. The aim of this work was to characterize Fe affected oxidative metabolism on the respiratory tissues of Mya arenaria. After 9 days of exposure to elevated Fe levels (500 μM of Fe as Fe-EDTA), a significant increase in the total Fe and labile Fe pool content was found in the gills. Dichlorofluorescein diacetate oxidation rate was higher after 17 days of exposure as compared to controls. Thiobarbituric acid reactive substances content increased 1.9- and 3.7-fold over controls on day 9 and 17, respectively. Both, catalase activity and nitrate and nitrite content decreased significantly on days 9 and 17 compared with controls. Similar effects were observed in mantle, but catalase activity was not affected. The results showed that in respiratory tissues the labile Fe pool is critically controlled to avoid radical-dependent cellular deterioration, but when the endogenous protection mechanisms are overwhelmed, tissue injury was observed.