<p>Melioidosis sepsis, caused by <i>Burkholderia pseudomallei</i>, is associated with high mortality due to an overwhelming inflammatory response. Plasmacytoid dendritic cells (pDC) are potent producers of type I interferons (IFN). This study investigated whether pDC and type I IFN play a role during the early stages of <i>B. pseudomallei</i> infection. Human and murine pDC internalised and killed <i>B. pseudomallei</i> as efficiently as murine conventional DC (cDC). pDC derived from <i>B. pseudomallei</i>-susceptible (BALB/c) mice demonstrated poor intracellular killing and increased IFN-alpha compared to pDC derived from <i>B. pseudomallei</i>-resistant (C57BL/6) mice. This is the first evidence of pDC bactericidal activity against <i>B. pseudomallei</i> infection.</p>