Intragastric inoculation of Klebsiella pneumoniae can cause invasive diseases, including necrosis of liver tissues and bacteremia. The effect of concanavalin A (ConA) on K. pneumoniae was tested. Pretreatment with ConA was able to protect mice from K. pneumoniae infection in an intragastric model. K. pneumoniae-induced mouse death and liver injury such as liver necrosis, as well as blood levels of aspartate aminotransferase and alanine aminotransferase, were inhibited in a dose-dependent manner by ConA. ConA administered intravenously as late as 24 h after K. pneumoniae inoculation was still protective. In an in vitro assay, ConA was able to bind K. pneumoniae cells directly and further agglutinate them but had no effect on their in vitro growth. Surveys of bacterial counts of ConA-treated mice revealed that the bacteria were eliminated effectively in both blood and liver tissues. Furthermore, the bactericidal activity of macrophages against K. pneumoniae was also enhanced in a dose-dependent manner by ConA in an in vitro culture. These data suggest that ConA is a potentially therapeutic agent for K. pneumoniae-induced liver infection.