Human cytomegalovirus (CMV) is a β‐herpesvirus that causes a chronic subclinical infection in healthy man. The immune system is unable to eliminate the virus completely, allowing virus to persist in a latent state. In the immunocompromised host, this equilibrium is disturbed, resulting in a clinical infection. In immunocompromised rats, clinical CMV infection is associated with an increase in NK cells and CD8⁺ T cells, including a phenotypically aberrant CD8⁺ T cell population. Using flow cytometry, we examined the effect of acute CMV infection on the composition of leukocyte subsets in immunocompromised patients. Therefore, we used peripheral blood of CMV seronegative patients receiving a kidney from a seronegative (control group) or a seropositive donor. Of the patients receiving a seropositive kidney, only the patients undergoing acute CMV infection were included (experimental group). Special attention was paid to the phenotype of the cytotoxic T cells. The development of acute CMV infection resulted in an increased NK cell number and an activation of both CD4⁺ and CD8⁺ T cells, as determined by HLA‐DR expression. An aberrant CD8⁺ T cell subset with decreased expression of CD8 and TCRαβ appeared in the infected patients. Furthermore, the size of this subpopulation of CD8⁺ T cells is positively correlated with the viral load.