Human cytomegalovirus (hCMV) is a prevalent virus that affects a large proportion of the populationworldwide. Natural Killer (NK) cells are essential immune cells that play a crucial role in controlling hCMVinfection. Despite the wide spread of hCMV infection, there is still not enough data related to the associationbetween innate and adaptive immunity. This study investigated the coordination between some of the NK cellmarkers expression and humoral immune response during hCMV infection. Thirty-three samples obtained fromdifferent healthy donors were investigated. The anti-hCMV IgG antibody titer was measured in serum samples,and expression of NKG2C, HLA-DR, CD57, KIR2DL2/DL3, and KIR2DL1 were analyzed in CD56+CD3-cells in PBMC samples by flow cytometry. To evaluate the dependence of proportions of different NK cell subsetson IgG titers, cluster analysis was first performed on all the obtained data, resulting in the identification of fourmain clusters. The identified clusters demonstrated a dependence on the levels of hCMV antibodies, accordingto which clusters corresponding to seronegative and low-positive were grouped. The results confirmed thathCMV infection leads to an expansion of NK cell populations expressing the NKG2C marker, which correlateswith higher levels of IgG response to hCMV. Besides, we identified increased HLA-DR+ and decreased ofKIR2DL1+ NK cells proportions in the middle anti-CMV-IgG level group compared to samples obtainedfrom seronegative and low-positive donors. Moreover, the statistically significant negative correlation wasfound between KIR2DL1+NK cell percentage and anti-CMV IgG antibody titer, while the positive correlationbetween HLA-DR+NK cell proportion and the IgG level was noticed only without the cluster correspondedto high level of anti-hCMV IgG. In this cohort, we did not find any association between KIR2DL3 and CD57expression in NK cells and levels of IgG response to hCMV. This may indicate that different subsets of NKcells may have distinct roles in regulating humoral immunity to hCMV. Overall, the results of the study providevaluable insights into the coordination of NK cell marker expression and IgG response in hCMV infection.