Hypernatremia is defined as plasma Na+ concentration above 145 meq/L (often due to absolute body water loss and not to total sodium excess). Nevertheless, when kidney damage is present, as occurs in renal diseases, hepatic cirrhosis and congestive heart failure, total body sodium can be increased. The present study evaluates the relationship between hypernatremia and response to anesthetic drug ketamine. For this purpose, 3 groups of rats, each consisting of 5 male Wistar rats ,weighing 200 ± 20 g, were chosen for the experiment. The control group used Zanjan city water during the study while the other two groups were maintained on 1% and 2% NaCl solutions. After 2 weeks, the response to anesthetic drug, ketamine (125 mg/kg) was studied. Results: The average serum sodium level in the rats of control group was 131 meq/L. For those on 1 and 2 percent solutions it was 148 meq/L and 165 meq/L. Sensitivity to the anesthetic drug, the speed of recovery from different stages of anesthesia and its total time was significantly increased in the test groups in comparison with the control group. This rise was quite conspicuous in those using 2 percent solutions. The mortality rate in the group using 1 percent solution was 20 percent and that of 2 percent solution was 60 percent. When hypernatremia develops, due to dehydration or any other reason, the anesthetic drug dosage should be reduced because hypernatremia increases the sensitivity to anesthesia and lengthens the recovery time from different stags of it. If the dose reduction is not practiced in hypernatremia, the increased mortality and drug side effects will most probably be encountered.