Background: Cancer cells support their growth and invasion by rewiring their metabolism. Therefore our aim was to explore the value of some metabolic mediators such as serum Fatty Acid Synthase (FASN) level and Lactate Dehydrogenase (LDH) activity as well as CEA, CA19-9 and plasma miR-181a levels as diagnostic markers and evaluating their relationship to the clinicopathological features in colorectal cancer (CRC) patients. The association of fasting blood sugar (FBS) and triglyceride (TG) levels as risk factors for colorectal cancer was also assessed. The study was conducted on 70 colorectal cancer patients and 30 controls. Results: CEA, CA19-9, FASN and miR-181a levels were significantly higher in sera of CRC patients compared to controls. miR-181a levels increased significantly according to stage and grade while CA19-9 increased significantly with grade not stage. LDH activity didn't show significant difference between CRC patients and control except for stage IV. CA19-9 and FASN were significantly increased among males while miR-181a was significantly elevated in female patients. None of the markers showed significant difference according to tumour site. Weak positive and negative correlations were observed between FASN and TG, between LDH and FBS respectively. Moreover, moderate and strong positive correlations were observed between miR-181a and FBS, between CEA and CA19-9 respectively. Conclusion: FASN showed the best diagnostic value with 96% sensitivity and 95% specificity followed by miR-181a with 95% sensitivity and 90% specificity; both were superior to LDH, CEA and CA 19-9. Moreover, miR-181a had the best association with stage and grade compared to all other studied markers.