This study investigates the association between sepsis and changes in host innate and adaptive immunity, aiming to identify potential mechanisms for immunosuppression. The research was conducted on 40 patients who died in intensive care units (ICUs) with severe sepsis, compared to control groups of brain-dead patients and those with emergent splenectomy due to trauma. The study found that splenocytes from sepsis patients had significantly reduced cytokine secretion compared to controls, with a decrease in tumor necrosis factor, interferon γ, interleukin 6, and interleukin 10. Flow cytometric analysis revealed increased expression of inhibitory receptors and ligands, as well as expanded suppressor cell populations in both spleen and lung tissues. Immunohistochemical staining showed extensive depletion of immune effector cells in spleen tissue and increased expression of ligands for inhibitory receptors on lung epithelial cells. These findings suggest that patients who die in the ICU following sepsis exhibit biochemical, flow cytometric, and immunohistochemical evidence of immunosuppression, indicating that targeted immune-enhancing therapies may be beneficial for selected patients with sepsis.This study investigates the association between sepsis and changes in host innate and adaptive immunity, aiming to identify potential mechanisms for immunosuppression. The research was conducted on 40 patients who died in intensive care units (ICUs) with severe sepsis, compared to control groups of brain-dead patients and those with emergent splenectomy due to trauma. The study found that splenocytes from sepsis patients had significantly reduced cytokine secretion compared to controls, with a decrease in tumor necrosis factor, interferon γ, interleukin 6, and interleukin 10. Flow cytometric analysis revealed increased expression of inhibitory receptors and ligands, as well as expanded suppressor cell populations in both spleen and lung tissues. Immunohistochemical staining showed extensive depletion of immune effector cells in spleen tissue and increased expression of ligands for inhibitory receptors on lung epithelial cells. These findings suggest that patients who die in the ICU following sepsis exhibit biochemical, flow cytometric, and immunohistochemical evidence of immunosuppression, indicating that targeted immune-enhancing therapies may be beneficial for selected patients with sepsis.