Abstract Depending on their protective properties against different cases of Colorectal Cancer (CRC), vitamins C, D, and E are the main focus of this research. CRC is one of the global public health concerns. 30 healthy individuals provided serum samples, whereas the group of CRC patients was divided into three, totaling 90 individuals. Group I consisted of 30 newly diagnosed cases of CRC. Group II 30 consisted of consisted of 30 CRC patients who were administered three cycles of chemotherapy. Group III consisted of 30 diagnosed CRC patients who also have non-alcoholic fatty liver disease (NAFLD). The concentrations and groups of vitamins C, D, and E were evaluated using ELISA. The levels of Vitamin C were significantly lower (p <0.0001) in individuals newly diagnosed with CRC, as compared to the control group. Patients who were recently diagnosed and treated for CRC and NAFLD exhibited comparable amounts of vitamin C. The level of vitamin E in control, newly diagnosed CRC and treated CRC patients displayed no significant differences, however comparing with newly diagnosed patients that suffered NAFLD, a significant decrease (p = 0.0014) in the level of vitamin E in CRC with NAFLD group was. The levels of Vitamin D in all groups of patients with colorectal cancer were significantly lower than those in the control group (p <0.0001). Colon cancer patients exhibited significantly decreased levels of vitamin C and D compared to healthy individuals. Vitamins showed potential as diagnostic markers for distinguishing between groups. It is necessary to analyze these findings as the level of serum vitamins may have potential use in the prognosis of the CRC in patients.