Introduction: Cytomegalovirus (CMV) infection is a common beta-herpesvirus infection widely spread in the human population. The proportion of infected population increases with age and approaches 100 % in elderly people. The infection is usually latent but is capable of reactivation when immunosuppression develops. The mechanisms of reactivation are not fully understood. The objective of our study was to evaluate the role of soluble molecules CD25, CD38, CD95 in the development of immunosuppression in CMV infection. Materials and methods: We used 18 serum samples from cases of CMV disease in the stage of reactivation, all confirmed by clinical and laboratory data. The patients received treatment in Nizhny Novgorod Infectious Disease Hospital No. 2. The serum content of the total and oligomeric soluble molecules CD25, CD38, and CD95 was identified by ELISA using monoclonal and polyclonal antibodies against human peripheral blood mononuclear cell proteins. The results were recorded spectrophotometrically and evaluated by converting optical density units to conventional units (U/mL). Results: We established an increase in the serum content of total and oligomeric fractions of soluble molecules CD25, CD38, and CD95 in the cases of CMV disease. While the serum content of the total and oligomeric fractions of molecules CD25 and CD38 increased equally, the oligomeric fraction of molecules СD95 demonstrated a more pronounced increase compared to the total fraction of these molecules. Our findings suggest the immune response suppression mechanism associated with initiation of apoptosis of effector T lymphocytes involving oligomeric form of molecules CD95. Conclusion: Changes in the content, structural and functional state of soluble differentiating molecules CD25, CD38, and CD95 indicate their involvement in immunosuppression mechanisms in patients with CMV infection.