Background: Cytokines are secreted locally in response to surgery and may be released into the systemic circulation. Reactive oxygen species (ROS) production is involved in various inflammatory conditions. The aims of the study were to examine the magnitude of surgical stress on the modulation of immune response and ROS production. Methods: Patients undergoing low- and intermediate-risk surgery (n=32) were enrolled. Blood samples for tumor necrosis factor (TNF)α, interleukin (IL)1 and IL10 assays were obtained before anesthesia, immediately after extubation, at 24 and 72 h after surgery. Measurement in whole-blood cultures of ex vivo lipopolysaccharide (LPS) and Staphylococcus aureus Cowan (SAC)-stimulated production of cytokines was carried out. The pro-oxidant potency of the whole serum was assessed in human umbilical vein endothelial cells using a fluorescent probe after stimulation by the plasma collected at the same time intervals. Results: TNFα, IL1 and IL10 did not increase significantly after surgery in either group. Whole-blood cultures response to LPS and SAC stimulation decreased for IL1 at the end of surgery in the two groups and returned to normal within 24 h after surgery. LPS- and SAC-induced IL10 production increased significantly at 24 h in the low-risk surgery group. ROS production was greater after more stressful surgery and was correlated to morphine consumption. Conclusion: Cytokine release in the systemic circulation was not well correlated to the magnitude of surgical stress, whereas transient immune hyporesponsiveness was seen after moderately stressful surgery. ROS production might be a more accurate indicator of the severity of surgical trauma.