Objectives: The aim of this study was to evaluate the accuracy of serum C-reactive protein (CRP) and intraperitoneal CRP, interleukin-6, and tumor necrosis factor-alpha in early diagnostics of anastomotic leakage in the first 4 postoperative days after colorectal surgery. Methods: Between January 2023 and June 2023, one hundred patients with colorectal carcinoma were operated on with primary anastomosis. Ten patients had anastomotic leak (10%). Results: Based on serum CRP, a patient with a leak will be detected with a 78% probability on postoperative day 3 with values above 169.0 mg/L and on postoperative day 4 with values equal to 159.0 mg/L and above. Intraperitoneal CRP values greater than 56 mg/L on the fourth postoperative day indicate a 78% probability of a diagnosis of leakage. An anastomotic leak will be detected with a 70.0% probability based on an IL-6 value on the first day, at a cut-off value of 42,150. The accuracy of TNF-alpha in predicting anastomotic leak in the first two days is 70% at values higher than 78.00 on the first and 58.50 on the second postoperative day. Conclusion: In this study serum CRP proved to be the most accurate in predicting anastomotic dehiscence after colorectal surgery.