Sepsis is the major cause of death among patients in the Intensive Care Unit. Studies demonstrated that there is a closed relationship between the immune dysfunction and changes of spleen dendritic cells during the progression of sepsis. It is also characterized as a large amounts loss of spleen dendritic cells, changed patterns of cytokine expression, and adverse prognosis. Therefore, deeper investigation into the alterations occurred upon spleen dendritic cell might provide noval treating method against sepsis. This article reviews the emerging data indicating the key role of spleen dendritic cells in sepsis.