Background: The role and regulation mechanisms of the interleukin-6 and 10 (IL6 and IL-10) serum levels and the interaction between CD4+ and CD8+ lymphocytes with SARS-COV-2 IgM and IgG in the context of COVID-19 infection are not fully understood. Methods: This study was conducted on 45 COVID-19 patients and 45 healthy individuals. The IL-6 and IL-10 promoter methylation, IL-6 and IL-10 gene expression, SARS-COV-2 IgM, and IgG antibodies and CD4+ and CD8+ lymphocytes were studied by qMSP-PCR, Real-time PCR, ELISA, and flow cytometry techniques, respectively. Results: The male ratio and mean age of critically ill patients’ group were significantly higher in compared to controls (P< 0. 05). IL-6 gene expression and serum levels were significantly increased in patients compared to controls (P=0. 002, 0. 001), but IL-6 promoter methylation was not significantly decreased in patients (P=0. 835). The IL-10 promoter methylation and expression were not different between cases and controls (0. 326, 0. 455), but serum IL-10 levels were higher in patients (P< 0. 001). The CD4+ and CD8+ lymphocytes decreased (P< 0. 001) and mean SARS-COV-2 IgG increased (P=0. 002) in the patients compared to controls. Conclusions: The COVID-19 disease result in severe complications in men and elderly. The serum levels of interleukin-6 and 10 increases in COVID-19 infection, and the gene expression of these two interleukins underlying in this increase. The serum levels of IL-6, IL-10 and SARS-COV-2 IgG as well as CD4+ and CD8+ lymphocyte counts should be investigated to monitor patients and predict the course of disease.