Background: Clozapine is an  efficacious  antipsychotic drug particularly in schizophrenic patients refractory to other agents. Treatment with clozapine was reported to be associated with sudden death, myocarditis  and  hepatotoxicity  in  some  patients. Aim of the Work: This study was  conducted  to  investigate  the toxic  effect of clozapine on cardiac muscle  and  liver of  adult  male  albino rats and to  assess the  potential  protective  role of  selenium. Materials and Methods: This study  employed fifty adult male albino rats  randomly  divided into five equal groups. Group I: Control group, Group II received daily 1 ml of 0.1 M HCl, balanced in  phosphate  buffered saline intraperitoneally (i.p.), Group III received oral selenium (1.5 mg/kg), Group IV received Clozapine (25 mg/kg) i.p. daily and Group V received both clozapine and selenium. After 14 days, the liver and ventricular  myocardium of each animal were dissected and processed for light and electron microscopic  studies. Results: After clozapine administration, the  ventricular  myocardium  showed  fragmentation  and  separation of cardiac muscles with  diffuse mixed inflammatory cellular infiltrate. The Z-lines were irregularly oriented  with  rupture of mitochondrial  membranes and cristae.  The liver exhibited  extensive  inflammatory cellular infiltration around the portal areas and  vacuolated  hepatocyte cytoplasm with rupture of membranes and cristae of some mitochondria. Concomitant administration of selenium with clozapine displayed an  observable  protection  against  these  changes. Conclusion: Selenium may have a protective role against cardiotoxicity and hepatotoxicity induced by clozapine therapy