Children with clinical signs of immunocompromise have impaired functioning of the immune system. At the same time, the state of subpopulations of multifunctional neutrophil granulocytes (NG), which provide antiviral and antibacterial protection, in such patients has been poorly studied. Objective of the study: To assess the features of the transformation of the phenotype of the three most significant subpopulations of NG, their association with impaired phagocytic and microbicidal activity in immunocompromised children with atypical viral-viral co-infections and bacterial infections, and to clarify their differential diagnostic significance. Materials and methods of research: The phenotypes of NG subpopulations expressing CD64, CD32, CD16, CD11b receptors, phagocytic and microbicidal activity of NG were studied in the peripheral blood of 43 immunocompromised children of both sexes aged of 5–9 years old suffering from recurrent ARVI, atypical chronic mono – or mixed herpes virus infections (HVI) and purulent bacterial infection. 3 study groups were formed: 1st – repeated ARVI/HVI mono, 2nd – repeated ARVI/HVI mixed, 3rd – minor purulent infection (MPI) and a comparison group (20 apparently healthy children). Results: Different differentiated transformation of the phenotype of functionally significant subpopulations of NG associated with impaired functional activity of NG as well as with the incidence of viral co-infections (repeated ARVI and recurrent HVI mixed) and the severity of clinical manifestations of MPI has been identified in the studied groups. Conclusion. Еvaluation of the features of transformation of phenotype of NG subpopulations, their effector functions in immunocompromised children with atypical viral-viral co-infections and purulent bacterial infections, will allow in the future to optimize the methods of target immunotherapy aimed at remodulating the negatively transformed phenotype of NG subpopulations, correcting their dysfunctions and, thereby, significantly increase the clinical effectiveness of therapeutic and preventive measures. © 2021, Pediatria Ltd.. All rights reserved.