The spleen and liver are target organs of one of the most pathogenic bacteria known to man: Francisella tularensis, the causative agent of tularemia. The focus of this dissertation was to identify and characterize the immune cells that become activated during tularemia infection, as these could have an important role in the severity of the infection. Mice were infected with sublethal doses of F. tularensis live vaccine strain, and cells from various organs were analyzed by histology, flow cytometry and immunofluorescent microscopy. An immature myeloid cellular population rapidly accumulated in the liver, spleen and bone marrow during the acute tularemia infection. This population was characterized by co-expression of Gr-1 and CD11b markers and had the greatest increases of all cellular phenotypes compared to uninfected mice. Cells expressing Gr-1 and CD11b, also known as myeloid derived suppressor cells (MDSCs), have been associated with immune suppression in both infectious and non-infectious conditions but their role in F. tularensis infection had never been determined. MDSCs were purified by live cell sorting to follow ex vivo cellular differentiation. In the presence of granulocyte macrophage colony-stimulating factor, the cells differentiated into dendritic cells and mature macrophages. Purified MDSCs were adoptively transferred into mice infected with sublethal doses of F. tularensis. The passively transferred cells did not lead to increased mortality or severity of infection. Additionally, B cells appear to have a regulatory role in MDSC accumulation. Mice deficient in B cells had delayed bacterial clearance and increased pathology in the liver and spleen, associated with sustained accumulation of Gr-1⁺ CD11b⁺ cells when compared to wild type mice. In tularemia, an accumulation of MDSC appears to regulate the infection in its early stages and may provide a threshold for survival.