New coronavirus infection (COVID-19) is an acute respiratory disease caused by the SARS-CoV-2 coronavirus. Tixagevimab+cilgavimab has been developed for the prevention and treatment of COVID-19. The purpose of this research was to evaluate the safety of the use of the two-component drug of monoclonal antibodies to SARS-CoV-2 (tixagevimab+cilgavimab) for pre-exposure prophylaxis of the new coronavirus infection in children with rheumatic diseases (RDs). Materials and methods used: a single-center retrospective study with prospective stage had been carried out that included 300 pediatric patients aged 12 to 18 y/o with RDs. The safety of pre-exposure prophylaxis of COVID-19 was assessed based on the dynamics of clinical and laboratory parameters as well as the total indices of RD activity. The effectiveness of pre-exposure prophylaxis was assessed based on recording the incidence of the new coronavirus infection. Safety and effectiveness were assessed after 3, 6, and 9 months after the administration of tixagevimab+cilgavimab drug. Results: no statistically significant increase in RDs activity was registered during 9 months of observation after pre-exposure prophylaxis of COVID-19. On the contrary, in patients with various types of juvenile arthritis, systemic lupus erythematosus and juvenile ankylosing spondylitis during the observation period against the background of antirheumatic therapy, a statistically significant decrease in the activity indices was registered - JADAS71 (p<0.001, p=0.002, p=0.030), SELENA-SLEDAI (p<0.001, p=0.027, p=0.570) and JSpADA (p=0.009, p=0.205, p=1.000), respectively; in patients with juvenile dermapolymyositis, systemic sclerosis and systemic vasculitis - a tendency to decrease in activity indices - DAS (p=0.002, p=0.050, p=0.193), J4S (p=0.840, p=0.720, p=1.000), PVAS (p=0.120, p=0.230, p=1.000 for the new and p=0.360, p=1.000, p=0.860 for the constant attributes), respectively. The new coronavirus infection was suffered by 6/300 (2%) patients within 9 months after pre-exposure prophylaxis. Conclusion: pre-exposure prophylaxis of COVID-19 with the two-component drug of monoclonal antibodies to SARS-CoV-2 (tixagevimab+cilgavimab) may be considered as both effective and safe and can therefore be suggested to pediatric patients with RDs.