Epstein-Barr virus (EBV) is a member of the Herpesvirus Family and the causative agent of infectious mononucleosis. Cytokine concentrations in serum samples taken from patients with infectious mononucleosis were measured in order to identify the cytokines responsible for the pathogenesis of the disease. The concentrations of Tumor Necrosis Factor-Alpha (TNF-α), Interferon-Gamma (IFN-γ) Interleukin-1 (IL-1), IL-2, IL-10, and Transforming Growth Factor Beta (TGF-β) were measured using an Enzyme-Linked Immunoassay (ELISA). It was found that the serum levels of IL-1, IL-2, and IFN-γ were significantly high in patients with acute EBV infection compared with the serum levels in healthy controls. Similarly, the levels of TNF-α increased compared to the controls, but the increase was not statistically significant. No significant difference in IL-10 and TGF-β concentrations was found between the two groups. The data in this study suggest that cytokines may have a critical role in the pathogenesis of infectious mononucleosis.