Significance How blood stem cells within the bone marrow respond to infection is still unclear. Here we study if mitochondrial transfer from the stromal cells to blood stem cells is required for the rapid generation of leukocytes which are required for the immune system to respond to bacterial infection. We find that mitochondria are transferred to blood stem cells within 2 h of sensing infection and show that direct contact between stromal cells and blood stem cells is required for mitochondrial transfer to occur. The metabolic changes that follow mitochondrial transfer into hematopoietic stem cells underpin the rapid mammalian response to infection. Finally, we find that, if mitochondrial transfer is blocked, an increase in bacterial colonization in the mammalian system occurs.