This study investigates the immune status of patients who died of sepsis and multiple organ failure, comparing them with those who died from non-sepsis causes. The research involved postmortem analysis of spleen and lung tissues from 40 sepsis patients and 29 control patients. The findings reveal significant immunosuppression in sepsis patients, characterized by reduced cytokine production, increased expression of inhibitory receptors, and depletion of immune effector cells. Sepsis patients showed marked reductions in cytokine secretion compared to controls, with cytokine production in sepsis patients generally less than 10% of that in controls. Flow cytometric analysis showed increased expression of inhibitory receptors and expansion of suppressor cell populations in both spleen and lung tissues. Immunohistochemical staining revealed extensive depletion of splenic CD4, CD8, and HLA-DR cells and expression of ligands for inhibitory receptors on lung epithelial cells. These findings suggest that patients who die of sepsis have biochemical, flow cytometric, and immunohistochemical evidence of immunosuppression. The study highlights the potential for targeted immune-enhancing therapy in selected sepsis patients. The results indicate that sepsis leads to a shift from an initial hyperinflammatory state to a subsequent hypoinflammatory state with significant immunosuppression. The study also identifies potential mechanisms for immunosuppression, including the dominance of inhibitory over activating receptors, expansion of suppressive cell types, and induction of inhibitory ligands on both antigen-presenting cells and tissue parenchymal cells. These findings suggest that T-cell exhaustion may be an important immunosuppressive mechanism in sepsis. The study has important therapeutic implications, suggesting that targeted immune-enhancing therapies may be beneficial for patients with severe immune compromise. The study also highlights the need for further research to understand the mechanisms of immunosuppression in sepsis and to develop effective treatments.This study investigates the immune status of patients who died of sepsis and multiple organ failure, comparing them with those who died from non-sepsis causes. The research involved postmortem analysis of spleen and lung tissues from 40 sepsis patients and 29 control patients. The findings reveal significant immunosuppression in sepsis patients, characterized by reduced cytokine production, increased expression of inhibitory receptors, and depletion of immune effector cells. Sepsis patients showed marked reductions in cytokine secretion compared to controls, with cytokine production in sepsis patients generally less than 10% of that in controls. Flow cytometric analysis showed increased expression of inhibitory receptors and expansion of suppressor cell populations in both spleen and lung tissues. Immunohistochemical staining revealed extensive depletion of splenic CD4, CD8, and HLA-DR cells and expression of ligands for inhibitory receptors on lung epithelial cells. These findings suggest that patients who die of sepsis have biochemical, flow cytometric, and immunohistochemical evidence of immunosuppression. The study highlights the potential for targeted immune-enhancing therapy in selected sepsis patients. The results indicate that sepsis leads to a shift from an initial hyperinflammatory state to a subsequent hypoinflammatory state with significant immunosuppression. The study also identifies potential mechanisms for immunosuppression, including the dominance of inhibitory over activating receptors, expansion of suppressive cell types, and induction of inhibitory ligands on both antigen-presenting cells and tissue parenchymal cells. These findings suggest that T-cell exhaustion may be an important immunosuppressive mechanism in sepsis. The study has important therapeutic implications, suggesting that targeted immune-enhancing therapies may be beneficial for patients with severe immune compromise. The study also highlights the need for further research to understand the mechanisms of immunosuppression in sepsis and to develop effective treatments.