Abstract: It has been demonstrated that proinflammatory cytokines such as (TNF-α), interleukin (IL) 6 and IL-8 increase in patients with trauma, surgical trauma, sepsis burn 40 patients scheduled for major abdominal surgery under combined epidural general anesthesia in gynecologic Department in Kasr El-Aini Hospital were included in this study, patients age was ranged between 18-50 years, patients were ASA I and II. The patients were divided into 2 groups each group 20 patients, group 1 was received S (+) ketamine as a single preincision dose, while in II S (+) ketamine was received preincision and as a repeated doses, S (+) ketamine was injected as a single IV dose 0.5 mg kg-1 before incision in both groups and repeated 0.2 mg kg-1 doses at 20 min interval until 30 min before the end of the operation (In group 2, 20 patients only). This study reported that S (+) ketamine suppressed TNF-α production IL-6, IL-8. The study also reported that a single S (+) ketamine preincision dose decreased IL-6 to 550±20 at 30 min before end of operation while the repeated 20 min doses decreased IL-6 to 440±20 min. IL-8 when single dose of S (+) ketamine was given decreased to 850±50 at 30 min before the operation, while after repeated S (+) ketamine it was 600±40 at 30 min before operation end, about TNF-α. It decreased to reach 1110±180 in a single dose of S (+) ketamine while it decreased to 1000±120 in repeated dose of S (+) ketamine. The total dose of S (+) ketamine was 35±30 in single dose group, while it was 80±40 in repeated dose group, the dose of ropivacaine given epidurally was 148±20 in single group while it was 130±15 in repeated group. The conclusion of the study was S (+) ketamine directly suppresses proinflammatory cytokines production when given in repeated doses; it also decreased the ropivacaine dose needed more in repeated doses of S (+) ketamine.