Objectives and background: Cytokines are important hormonal mediators, produced in tissues undergoing defense, growth and repair processes. Infection and inflammation in particular result in a cascade of cytokine induction that acts to maintain tissue homeostasis. Most cytokines act within the injured tissues, although some have an endocrine action, recruiting distant tissues in defense of the tissue producing the cytokine and many are important for regulating acquired immunity in secondary lymphoid tissues. It has been demonstrated that proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) increase in patients with trauma, surgery, sepsis and burns. Methods: 60 patients scheduled for radical cystectomy under combined epidural general anesthesia in Kasr El-Aini hospital were included in this study, patients’ ages were ranged between 44 – 61years, and patients were ASA І and ІІ. Patients were divided into 3 groups each 20 patients, group І received no S (+) ketamine (control group), group ІІ received S (+) ketamine as a single preincision dose and group ІІІ received preincision and as repeated doses of S (+) ketamine. S (+) ketamine was injected as a single IV dose of 0.5 mg/kg in group ІІ and ІІІ, repeated as 0.2 mg/kg at 20 minutes interval until 30 minutes before end of surgery (in group ІІІ only, 20 patients only). Results: this study reported that S (+) ketamine suppressed TNF-α and IL-6 production. The study also reported that a single preincision dose of S (+) ketamine decreased TNF-α to reach 1110±180 ug/ml and IL-6 to reach 550±20 pg/ml while the repeated doses of S (+) ketamine decreased TNF-α to reach 1000±120 ug/ml and IL-6 to reach 440±20 pg/ml. The total dose of S (+) ketamine was 70±20 mg in single dose group 100±50 mg and the total dose of ropivacaine given epidurally was 160±20 mg in the single dose group, while it was 130±15 mg in the repeated dose group. This mean the anesthetics required in repeated doses of S (+) ketamine group was lower, indicated that S (+) ketamine decreased the anesthetic requirements. Conclusion: S (+) ketamine directly suppresses proinflammatory cytokines production especially when given in repeated doses; it also decreased the ropivacaine dose needed more in repeated doses of S (+) ketamine. A larger study is also needed to assess whether the favorable postoperative effect of S (+) ketamine make difference or not in clinical outcomes such as; time to ambulation, resumption of dietary intake, discharge from hospital, and cost/benefit when S (+) ketamine is used.