The obligate intracellular bacteria， Rickettsia rickettsii and Coxiella burnetii， are the potential agents of bio-warfare/bio-terrorism. Here C3H/HeN mice were immunized with a recombinant protein fragment rOmp-4 derived from outer membrane protein B， a major protective antigen of R. rickettsii， combined with chloroform-methanol residue (CMR) extracted from phase I C. burnetii organisms， a safer Q fever vaccine. These immunized mice had significantly higher levels of IgG1 and IgG2a to rOmpB-4 and interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α)， two crucial cytokines in resisting intracellular bacterial infection， as well as significantly lower rickettsial loads and slighter pathological lesions in organs after challenge with R. rickettsii， compared with mice immunized with rOmpB-4 or CMR alone. Additionally， after challenge with C. burnetii， the coxiella loads in the organs of these mice were significantly lower than those of mice immunized with rOmpB-4 alone. Our results prove that CMR could markedly potentiate enhance the rOmpB-4-specific immunoprotection by promoting specific and non-specific immunoresponses and the immunization with the protective antigen of R. rickettsii combined with CMR of C. burnetii could confer effective protection against infection of R. rickettsii or C. burnetii.