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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to a pandemic in March 2020. During a viral infection, it has been reported that epigenetic changes occur for both sides: Infected cells elicit an antiviral environmental response, which induces and initiates certain pathways for proper response to the virus, while the virus silences the expression of vital genes in the anti-viral host cell. In this study, we aimed to examine the methylation level of the MX1 gene promoter in different stages in COVID-19 patients compared to the control group.In total, 470 COVID-19 patients with a positive polymerase chain reaction (PCR) test (235 women and 235 men) were recruited into the study as the test group. Patients were divided based on the World Health Organization (WHO) classification into three groups: moderate, severe, and critical. Moreover, 100 healthy individuals (50 women and 50 men) were selected as the control group. Peripheral white blood cells were collected and PCR was performed using two types of primers designed for methylated and unmethylated states of the MX1 gene. The PCR products were then loaded on agarose gel and the band intensities were calculated by ImageJ software.The results showed a decrease in the methylation of the MX1 gene promoter in moderate and severe groups and an increase in the MX1 gene promoter methylation in the critical group. In addition, the level of methylation was higher in men than in women.Increased methylation of the MX1 gene in the critical group may indicate the role of SARS-CoV-2 in reducing the expression levels of this antiviral gene and thus promoting virus replication and disease progression.