Objective. To assess the association between clinical and laboratory characteristics of infectious mononucleosis (IM) and disease etiology and phase of infection. Patients and methods. This prospective observational study was conducted at Z.A.Bashlyaeva Children's City Clinical Hospital, Moscow Healthcare Department and included 107 children with IM. Laboratory testing was performed at the Department of Virological Diagnostics, National Medical Research Center for Hematology, Ministry of Health of the Russian Federation. Results. IM is a polyetiologic disease. So far, researcher have failed to find a significant correlation between clinical manifestations of IM and its etiology and phase of infection. Patients with IM caused by primary monoinfection with Epstein–Barr virus (EBV) are at high risk of developing chronic EBV infection. Neutrophilia is a typical laboratory sign of IM during the acute phase of it. Conclusion. The improvement of IM diagnosis with a detailed evaluation of clinical and laboratory criteria, as well as risk assessment of unfavorable outcome are currently impossible without the identification of both disease etiology and phase of infection. © 2020, Dynasty Publishing House. All rights reserved.