Sepsis is a common complication of severe injuries, such as severe infection, trauma, burn, and shock, and it is the main cause of death of critically ill patients. Endotoxemia caused by lipopolysaccharides (LPS), cell wall components of gram-negative bacteria, is one of the main causes of sepsis. Multiple plasma proteins, including lipopolysaccharide binding proteins ( LBP ) and bactericidal permeability increase proteins ( BPI ), are involved in regulating the signaling pathways of LPS activation. The two proteins belong to the same family of proteins with similar structures but different biological functions: LBP facilitates LPS in binding to the CD14 receptor of target cells to increase host sensitivity to LPS, while BPI neutralizes the inflammatory effects of LPS and accelerates the clearance of LPS from the circulation. In this review, we summarized the research progress of LBP and BPI in terms of structure, function, potential for treatment of sepsis, and the correlation between gene polymorphisms and sepsis.