The aim:Colorectal cancer is among the most common tumors in humans. According to the frequency of cancer it is in the third place (behind lung and breast cancer) and is the second leading cause of mortality in developed countries. Postoperative pain is a inevitableconsequence of extensive surgery and takes rise withthe activation of the nervous system for the conduction of pain (nociceptive system), tissue injury or inflammation. As a result of tissue injury, many different mediators are released from damaged tissues, immunocompetent cells, sympathetic and sensory fibers which directly or indirectly activate nociceptors. Postoperative pain leads to the suppression of the immune system, including reduced activity of NK cells, cytotoxic T lymphocytes and macrophages. Surgical stress and postoperative pain accelerates apoptosis of certain lymphocyte subpopulations leading to increased risk of developing postoperative complications. In the treatment of postoperative pain after colorectal cancer surgery, the most common techniques are: application of opioid intravenous analgesia and epidural analgesia, which implays the application of analgesics in the epidural space of medulla spinalis through a catheter, where it blocks the spinal nerve roots. Opioid analgesics are very effective in treating postoperative pain, but it leads to the suppression of the immune system, increasing the risk of the development of infection and dissemination of tumor cells. Patients and Methods: We examined the effects of epidural and intravenous analgesia in patients after colorectal cancer surgery on the immune system. We analyzed the phenotype of isolated peripheral blood mononuclear cells of patients and volunteers by flow cytometry after intracellular and surface staining. The ability of killing of peripheral blood mononuclear cells You created this PDF from an application that is not licensed to print to novaPDF printer (http://www.novapdf.com) VIIIagainst NK-sensitive cell lines was tested in two-hour test of cytotoxicity. Statistical data were calculated by a computer program Statistica 7.1. Graphical and tabular presentation was made in the Excel program. Results: Application of intravenous analgesia on the first postoperative day leads to a statistically significant decrease in NKT cells. Low values of Tregs were expressed in the first and sixth postoperative day. Intravenous analgesia resulted in a statistically significant decrease in total perforin first and sixth postoperative day, and in the reduction of double positive cells: CD3+P+, CD4+P+ and CD8+P+. Intravenous analgesia has led to a statistically significant reduction of cytotoxicity of lymphocytes from peripheral blood of patients with colorectal cancer compared to epidural analgesia in the two-hour test cytotoxicity toward NK-sensitive K - 562 cell line. Conclusion: Intravenous analgesia after colorectal cancer surgery has led to a statistically significant greater depression of innate and acquired immunity, as well as cytolythic activity of peripheral blood mononuclear cells in comparison to epidural analgesia