The postoperative period is accompanied with neuroendocrine, metabolic and immune alteration which is caused by tissue damage, anesthesia, postoperative pain and psychological stress. Postoperative pain contributes to dysfunction of immune response as a result of interaction between central nervous and immune system. The postoperatively activated hypotalamo–pituitary–adrenocortical axis, sympathic and parasympathic nerve systems are important modulators of immune response. According to bidirec tional communication of immune and nervous system, appropriate postoperative pain management could affect immune response in postoperative period. Although the postoperative suppression of immune response has been reported, a very little are known about the influences of different pain man agement techniques on cytotoxic function of immune cells in patients with colorectal cancer in early postoperative period. Perforin is a cytotoxic molecule expressed by activated lymphocytes which has a crucial role in elimination of tumor cells and virus-infected cells, mostly during the effector’s phase of immune response. Immune compromise during the postoperative period could affect the healing pro cesses, incidence of postoperative infections and rate and size of tumor metastases disseminated during operation. The pharmacological management of postoperative pain in patients with malignancies uses very different analgesic techniques whose possible influence on cytotoxic functions of immune cells are still understood poor. For decades the most common way of treating postoperative pain after colorec tal cancer surgery was intravenous analgesia with opiods. In the last decade many investigations pointed out that opiods can also contribute to postoperative suppression of immune response. Epidural analgesia is a regional anesthesia technique that acts directly on the origin of pain impulses and pain relief can be achieved with small doses of opiods combined with local anesthetics. Local anesthetics potentate analgesic properties of opiods but per se are also acting as antiinflammatory drugs. Afferent neural blockade by epidural analgesia attenuates neuroendocrine stress response. We propose that epidural analgesia could be more convenient that intravenous analgesia in maintenance of immunological homeo stasis that is altered by surgical stress, tumor growth and pain.