Microcystins (MCs) are potent hepatotoxins produced by cyanobacteria in water systems that induce oxidative stress in fish. The present study investigated the effect of vitamin E pretreatment on MC-induced oxidative damage in the liver, kidneys, and gills of tilapia fish (Oreochromis niloticus). Groups of fish were fed vitamin E supplements (200 or 700 mg per kilogram of diet) for 7 d or received only commercial fish food and then were exposed to a single oral dose of cyanobacterial cells (120 microg of MC-LR [2:Leu, 4:Arg] per fish), and were sacrificed in 24 h. The potential benefits of vitamin E were evaluated based on lipid peroxidation (LPO), protein oxidation, catalase (CAT, Enzyme Commission [EC] 1.11.1.6), superoxide dismutase (EC 1.15.1.1), glutathione peroxidase (EC 1.11.1.9), glutathione reductase (EC 1.8.1.7), and the ratio of reduced glutathione to oxidized glutathione (GSH/GSSG). Microcystins induced a 1.6-fold increase in LPO values in liver, whereas vitamin E-pretreated fish showed no alteration on this biomarker. Enzyme activities levels were also ameliorated by the chemoprotectant, whereas protein oxidation and GSH/GSSG did not show any significant change. The higher vitamin E dose used proved to have the greater protective effects, particularly on the biomarkers LPO and CAT. The results show that vitamin E could have a potential use as a preventive or therapeutic measure in MC-exposed fish.