Vaccination strategies against Klebsiella pneumoniae have largely focussed on the polysaccharide capsule. However, the large number and high prevalence of individual capsular serotypes limits the widespread applicability of capsule-based vaccines. This study establishes that immunization with purified LPS can protect mice against lethal challenge with K. pneumoniae, and that subcapsular antibodies directed against purified LPS can be used to treat and/or prevent experimental K. pneumoniae infection in mice. This approach offers potential for prophylaxis and/or therapy against drug-resistant strains of K. pneumoniae.