Sepsis is a serious infectious life threatening disease. In this study, we demonstrate that LII-34, a natural compound isolated from garlic (Allium sativum L.), markedly enhances survival rate, by inhibiting lung inflammation in cecal ligation and puncture (CLP) experimental polymicrobial sepsis model. LII-34 strongly reduced bacterial colony unit from peritoneal fluid in CLP mice by stimulating generation of reactive oxygen species. Lymphocyte apoptosis from spleen in CLP mice was also markedly decreased by LII-34 administration. LII-34 also significantly inhibits the production of proinflammatory cytokines such as TNF-α, interleukin-1β (IL-1β) and IL-6 in CLP mice. Lipopolysaccharide-stimulated the production of TNF-α, CCL2, IL-6, and IL-10 are also strongly inhibited by LII-34 in mouse bone marrow-derived macrophages. Taken together, our results indicate that LII-34 shows therapeutic effect against polymicrobial sepsis by enhancing microbial killing and blocking cytokine storm. Chang Youp Ok and Sung Kyun Lee are equally contributed to this work.