Background: Anastomotic leak (AL) is the most common unfavorable complication after colorectal surgery. Early discharge benefits the patient but carries a potential risk of developing AL. So the early diagnosis of AL is critical. Aim: To assess whether C-reactive protein (CRP) and Procalcitonin (PCT) will predict AL before early discharge. Methods: This study was carried out in Surgical-oncology Unit, General Surgery Department, Zagazig University Hospitals, during the period from May 2018 to November 2018. The study included 24 patients with Colorectal cancer undergoing elective open colorectal resection with anastomosis. CRP and PCT were measured pre-operatively, 8h after incision, and on the 3rd and 5th postoperative day (POD). 30-day readmissions, re-laparotomy, and mortality were recorded. Results: 5 patients had AL (20.8%). 5th day postoperative CRP and PCT were significantly lower in patients without AL than patients with AL. The present study revealed the diagnostic performance of CRP in the prediction of AL where 5th day CRP>198.23mg/mL had 100% sensitivity, 94.74% specificity, 83.3% positive predictive value, 100% negative predictive value and 95.8% accuracy in the prediction of AL. Also, the study revealed diagnostic performance of 5th day PCT in the prediction of AL where a cutoff of more than 1.212 ng/dl, 5th day PCT had 80% sensitivity, 100% specificity, 100% positive predictive value, 95% negative predictive value and 95.8% accuracy in prediction of AL. Conclusion: CRP and PCT measurements can positively identify patients at risk of AL with CRP being more accurate and a potentially powerful marker.