Aim: The purpose of this study was to investigate the protective effects of ethyl pyruvate (EP) and dimethyl sulfoxide (DMSO) on ischemic tissue in brain and cardiac and hepatic tissues in experimentally induced carbon monoxide (CO) intoxication. Material and Methods: Thirty-five mature female Sprague Dawley rats were randomized into five groups of seven animals each. Group 1 received no CO or treatment. Rats in groups 2, 3, 4 and 5 were made to inhale a high-concentration 5000 ppm CO gas mixture for 60 min at 4 L/min. CO levels were then measured from 1 mL tail vein blood. Group 2 received no therapeutic agent, group 3 received 6 mg/kg intraperitoneal (ip) DMSO, group 4 received 50 mg/kg ip EP, group 5 received 50 mg/kg EP and 6 mg/kg DMSO ip. All rats were sacrificed by decapitation. Brain, cardiac and hepatic tissues were removed and histopathological scores were compared. Results: Comparison of group 2 with group 3 and group 2 with group 5 revealed that DMSO alone and EP + DMSO exhibited a reducing effect on degree of cerebral neuronal alteration, degenerative neuron rates, and total cardiac injury score (p=0.005, p=0.002, p=0.004 and p=0.002, p=0.001, p=0.004 respectively). There was no histopathological difference between group 2 and group 4 suggesting EP alone had no therapeutic effect on histopathological injury. Conclusion: Based on our study findings, EP administered alone exhibited no protective effects on the organ injuries investigated, while DMSO exhibited reducing effects on degree of neuron alteration, rates of degenerative neurons, and total cardiac injury scores. An ameliorating effect on cardiac and hepatic injury was more prominent with combined treatment.