Introduction. In 2020, most doctors were at the frontlines in the fight against the novel coronavirus infection (COVID-19). In the process of searching for effective etiotropic drugs, news came in that type I interferons had been successfully used for the treatment of COVID-19. Choosing the optimal COVID-19 treatment strategy is of pivotal importance for vulnerable populations such as children. Objective of the study. To show our own experience in providing medical care to children with COVID-19 and present the results of a comparative study of the efficacy and safety of interferon alfa-2b drugs combined with highly active antioxidants in the complex COVID-19 therapy in children. Materials and methods. A comparative study of the efficacy and safety of interferon alfa-2b drugs combined with highly active antioxidants in the complex COVID-19 therapy in children was conducted. The study included children with a laboratoryconfirmed diagnosis of COVID-19 aged 1 - 17 years (n = 85). In the treatment group (n = 45), children received interferon alfa-2b drugs such as VIFERON® rectal suppositories and VIFERON® gel for topical administration according to the dosage regimen and standard therapy. In the control group (n = 40), children only received standard therapy in accordance with the recommendations of the Ministry of Health of Russia. Results and discussion. 3,696 patients, including 3,507 children, received medical care in the City Children’s Hospital No. 1 in Kazan since April 2020. The share of laboratory-confirmed COVID-19 cases among admitted children was 21% (n = 736), of which 85 were enrolled in the study to assess the efficacy of complex therapy with interferon alpha-2b drugs combined with highly active antioxidants. The interferon alfa-2b therapy of COVID-19 children reduced the duration of the key clinical symptoms of the disease by 1.5-4 days and the virus elimination time by 6 days. Conclusions. The use of interferon alfa-2b VIFERON® rectal suppositories and VIFERON® gel for topical administration according to the dose regimen in combination with the standard therapy in COVID-19 children contributed to faster elimination of clinical symptoms of the disease and virus elimination compared to the standard therapy.