Epstein-Barr virus (EBV) belongs to the family of herpesviruses (herpes type 4) and is one of the most common and highly contagious. During the pandemic of a new coronavirus disease, it was found that in patients previously infected with EBV, COVID-19 can cause its reactivation, which is often manifested by the clinic of acute hepatitis. The article presents a clinical case of the development of acute hepatitis in a patient with mixed infection with EBV and SARS-CoV-2 in combination with allergic toxic reaction while taking sulfasalazine prescribed for spondyloarthritis. A feature of this case was the development of severe hepatitis of mixed genesis with a favorable outcome. The importance of adherence to drug monitoring rules for newly prescribed drugs for COVID-19 was emphasized. In severe cases of the disease, the possibility of mixed infection should be taken into account.