Aim: Free radicals play a key role in the development of degenerative diseases, none the less, effects of harmful reactive species can be controlled by natural defense mechanisms in the body. In this study, we aimed to investigate enzyme activities of superoxide dismutase (SOD), glutathione (GSH) reductase, glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) in blood serum samples of patients with colon cancer. Material and Method: This retrospective study included patients diagnosed with colon cancer (n=25) and age-and sex-matched healthy individuals as the control group (n=25). Serum levels of SOD, GSH, GSH-Px, and MDA were analyzed using the spectrophotometric method. Results: Enzyme levels of SOD, GSH, GSH-Px, and MDA were found to be statistically significantly (p< 0.05), compared to the control group. There was a significant increase in the MDA levels (p< 0.05), whereas the SOD, GSH, and GSH-Px levels decreased in the patients with colon cancer, compared to the control group (p< 0.05). MDA levels were significantly higher in the patients with colon cancer, while antioxidant enzymes including SOD, GSH, and GSH-Px activities were significantly lower in these patients, compared to the control group (p< 0.05). Discussion: Our study, for the first time, suggests a relationship between colon cancer, oxidative stress, and antioxidant parameters. This is also the first study to investigate the levels of oxidative stress levels and antioxidant enzymes such as SOD, GSH, and GSH-Px activities in the literature. Also, decreased GSH-Px activity may increase MDA production, suggesting that serum SOD, GSH, GSH-Px and MDA levels can affect the etiopathogenesis of colon cancer.