Aim: Changes in the metabolic, endocrine, and immune systems caused by surgical trauma and pain are associated with increased concentrations of the biological mediators such as cytokines. Preemptive epidural analgesia may affect pain caused by surgical trauma and the corresponding neurohumoral response induced by the neuromediators. This study investigated the effects of preemptive epidural analgesia on postoperative pain and cytokine levels. Methods: A total of 60 children undergoing urological surgery were randomly assigned to either the preemptive epidural analgesia (Preempt EA, n=31) group or the postoperative epidural analgesia (Postop EA, n=29) group. Epidural infusion was started before the surgical incision in Preempt EA group and after the peritoneal closure in the Postop EA group. Blood samples were collected preoperatively (before anesthesia induction), 1 h and 24 h after surgery. Plasma TNF-α and IL-2 levels were measured by ELISA. Postoperative pain was assessed using the FACES pain scale, and postoperative analgesia was evaluated 1 h and 24 h after surgery. Results: Although TNF-α levels were increased 1 h and 24 h after surgery compared to preoperative levels in both groups, the levels were significantly higher in the Postop EA group. IL-2 levels were significantly higher at both postoperative time points in the Preempt EA group than in the Postop EA group. There were no significant differences in pain scores between the groups. Conclusion: Our results suggest that preemptive epidural analgesia may attenuate the proinflammatory response but has no effect on pain intensity.