Colorectal cancer (CRC) is a leading cause of mortality worldwide. Its incidence holds a major position among the most common life-threatening diseases. Hence, the early identification and precise characterization of disease activity based on proper biomarkers are of utmost importance for therapeutic strategy and patient survival. The identification of new biomarkers for colorectal cancer or disease-specific levels/combinations of biomarkers will significantly contribute to precise diagnosis and improved personalized treatment of patients. Therefore, the present study aims to identify colorectal cancer-specific immunological biomarkers. The plasma levels of several cytokines (interleukin-1β /IL-1β/, IL-2, IL-4, IL-10, IL-12, IL-15, TGFβ and IFNγ) of 20 patients with colorectal cancer and 21 healthy individuals were determined by ELISA. The expression of several types of glycoproteins on the surface of peripheral blood leukocytes isolated from CRC patients and healthy volunteers was evaluated by flow cytometry. Correlations between cytokine levels and cell surface glycoprotein expression were analyzed. The obtained results demonstrated significantly elevated levels of CD80, CD86, CD279 and CD274 expressing leukocyte populations in the cancer patient group, while the numbers of NK cells and CD8- and CD25-positive cells were decreased. Based on these data and the correlations with cytokine levels, it can be concluded that CD25, CD80, CD86, CD274 and CD279 glycoproteins combined with specific plasma levels of IL-1β, IL-2, IL-15 and TGFβ could represent potential biomarkers for colorectal cancer.