Radiotherapy and chemotherapy compromise individuals’ immunity clinically, resulting in increased opportunistic infections. In this study, the cyclophosphamide-induced immunocompromised C57BL/6J mouse with Klebsiella infection was hired to analyze the effect of the active components of Acanthopanax senticosus on anti-infection for immunocompromised individuals. As a result, Acanthopanax senticosus polysaccharide (ASPS) was selected with the best effect. For immunocompromised C57BL/6J mouse, ASPS increased its indices of thymus and spleen, reducing the bacteria load in lung and protecting the function of liver. Meanwhile, ASPS obviously boosted the total number of thymocytes and the number of CD4+ T cells in spleen, promoting the proportions of CD4+ TCM and TEM cells, while decreasing that of CD4+ TEMRA cells in in peripheral blood. Moreover, ASPS enhanced the number of NF-κB+, CD192+ Mφ and NF-κB+ neutrophils in the abdomen and strengthened their antibacterial function, however, reduced the number of NF-κB+ Mφ and neutrophils in the spleen reducing inflammation. It is also observed by immunofluorescence that the NF-κB expression of peritoneal Mφ increased evidently after the mice were treated with ASPS. In conclusion, ASPS has an obvious effect against infection for immunocompromised mice by promoting immunity recovery.