Inhibitory receptors control the activation and differentiation of cells during the recognition of target antigens by sending co-inhibitory signals that regulate the strength of the immune response. Hemorrhagic fever with renal syndrome (HFRS) is a disease caused by Old World orthohantaviruses, and the most common causative agent in Europe is Puumala orthohantavirus. It is known that the immune response plays a role in the pathogenesis of HFRS. The aim of the study was to explore the association of LAG-3, TIM-3 and PD-1 receptor expression on CD8+ lymphocytes and natural killer cells and their serum concentrations with clinical parameters that indicate the severity of the clinical picture in patients with HFRS. Procartaplex multiplex immunoassay and flow cytometry were used to measure the expression of LAG-3, TIM-3 and PD- 1 receptors on CD8+ lymphocytes and natural killer cells and their concentrations in serum, and their association with clinical parameters indicating the severity of the clinical picture was examined. The results showed a higher expression of these receptors on CD8+ lymphocytes and natural killer cells and higher concentrations of their soluble forms in the serum of patients with HFRS compared to controls, and their association with clinical parameters. Additional research is needed to determine the causal relationship between the expression of LAG-3, TIM-3 and PD-1 receptors and the severity of the clinical picture and to further examine their role in acute infections.