Background Research in the subject of the influence of SARS-CoV-2 mechanisms on human’s homeostasis remains actual problem. Particular interest is the study of pathomorphological changes in the appendix in children with COVID-19. Objectives Aim of the study: morphological and molecular biological evaluation of the appendix in children of different age groups with COVID-19. Methods Groups were formed on the basis of anamnestic, clinical and morphological data: I (n = 42; aged 2 to 18 years, average - 10.8 years) – with an established clinical diagnosis: coronavirus infection (COVID-19; PCR+); II (n = 55; aged 2 to 18 years, average - 9.7 years) – with a confirmed clinical diagnosis of acute appendicitis; collected before the onset of the COVID-19 pandemic in 2017-2019; III (n = 38; aged 2 to 18 years, average - 10.3 years) - control group. Histological and immunohistochemical studies were conducted using primary antibodies to CD3, CD4, CD68, CD163, CD20, CD138 and to pro-inflammatory (IL-1, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines. Results In most samples of appendix in children with COVID-19 were discovered signs of destructive phlegmonous-ulcerative and gangrenous appendicitis. An increase in CD3+, CD4+, CD68+, CD163+, CD20+ CD138+ immunocompetent cells was found in the appendix of children with COVID-19. As well, there is an increase in pro-inflammatory (IL-1, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines. Conclusions The aforementioned pathological and immunohistochemical changes were more pronounced in the group of children aged 6-12 years (childhood).