ABSTRACT: Burn is one of the most common and devastating forms of trauma. Major burn injury disturbs the immune system, resulting in marked alterations in bone marrow hematopoiesis and a progressive suppression of the immune response, which are thought to contribute to increased susceptibility to secondary infections and the development of sepsis. Immunosuppression in patients with severe burn and sepsis leads to high morbidity and mortality in these patients. mononuclear phagocytes system (MPS) is a critical component of the innate immune response and plays key roles in burn immunity. These phagocytes are the first cellular responders to severe burn injury after acute disruption of the skin barrier. They are not only able to internalize and digest bacteria and dead cells and scavenge toxic compounds produced by metabolism, but also able to initiate an adaptive immune response. Severe burn and sepsis profoundly inhibit the functions of dendritic cells, monocytes, and macrophages. Adoptive transfer of MPS or stem cells to patients with severe burn and sepsis that aim to restore MPS function is promising. A better understanding of the roles played by MPS in the pathophysiology of severe burn and sepsis will guarantee a more rational and effective immunotherapy of patients with severe burn and sepsis.