This study was designed to investigate the protective effects of sodium selenite and/or vitamin E against mercuric chloride-induced cardiotoxicity. Male Wistar rats (n=48, 310 +/- 10 g) were administered mercuric chloride (1.0 mg/kg bw), sodium selenite (0.25 mg/kg bw), vitamin E (100 mg/kg bw), sodium selenite plus mercuric chloride, vitamin E plus mercuric chloride and sodium selenite plus vitamin E plus mercuric chloride daily via gavage for four weeks. Malondialdehyde (MDA) level, antioxidant enzyme activities [total superoxide dismutase (SOD), catalase (CAT), total glutathione peroxidase (GPx) and total glutathione-S-transferase (GST)], and histopathological changes in the heart tissue were evaluated. Results showed that mercuric chloride exposure resulted in an increase in the MDA level and a decrease in the SOD, CAT, GPx and GST activities, with respect to the control. Light microscopic investigations revealed that mercuric chloride induced histopathological changes in the heart tissue. A significant decrease in the MDA level and a significant increase in the SOD, CAT, GPx and GST activities were observed on the supplementation of sodium selenite and/or vitamin E to mercuric chloride-treated rats, which showed that, sodium selenite and/or vitamin E significantly reduced mercuric chloride induced cardiotoxicity, but not protected completely.