Background: The focus of this study was to understand the relationship between the failure of gut barrier function, inflammatory markers and septic complications after resection for extraperitoneal rectal cancer. Methods: One hundred seven patients were enrolled into this prospective observational study and underwent open colorectal resection for extraperitoneal cancer. All patients underwent an assessment of intestinal permeability (L/M ratio), endotoxemia, interleukin-1β (IL-1β), interleukin-6 (IL-6), C-reactive protein (CRP) and elastase levels before surgery and on postoperative days 1, 3, and 7. Results: Septic complications developed in 23.3% of patients. There were no significant differences in preoperative L/M ratio, endotoxine, CRP, interleukin-1 (IL-1), IL-6, and elastase levels between septic and non-septic groups. All patients showed a significant increase in intestinal permeability, endotoxemia, IL-1, IL-6, CRP, and elastase on the first postoperative day. At postoperative day 7, the septic group continued to demonstrate an increase in intestinal permeability, endotoxemia and elastase and significant difference was observed between the 2 groups (p < 0.05), whereas there was no significant difference in IL-1, IL-6, and CRP levels. Conclusion: The pattern of change in the postoperative period of intestinal permeability, systemic endotoxemia and elastase concentration is significantly higher in patients in whom sepsis develops, while the concentration of IL-1β, IL-6, and CRP does not permit to distinguish infection from inflammation.