Increase in the red blood cell mean corpuscular volume (MCV), and mean corpuscular haemoglobin (MCH) values in patients receiving Valproate as mono or polytherapy was noted. To investigate this situation 41 epileptic patients were studied on Valproate alone (Group 1) and 20 patients on Valproate added to another antiepileptic drug (AED), (Group 4), and compared with 19 patients on carbamazepine (CBZ) (Group 2) and 12 patients on phenytoin (PHT), (Group 3). The results showed significant rise in MCV values in Groups 1 and 4. The peripheral blood smear and other tests including reticulocyte counts of the patients with abnormal values ruled out macrocytic anemias. We postulate a generalized effect which is the result of alteration in erythrocyte membrane phospholipids.