Enterococcus faecalis is one of most frequently isolated bacterial species in wounds yet little is known about its pathogenic mechanisms in this setting. We have characterized a mouse excisional wound model to study the infection dynamics of E. faecalis and shown that infected wounds are associated with acute bacterial replication, long term persistence within the wounds, and delayed wound healing. Fluorescence-activated cell sorting of wound explants revealed viable E. faecalis within both CD45+ immune cells CD45- non-immune cells up to 5 days after infection. We have shown that lactic acid production by E. faecalis can actively suppress NK-kB signaling in CD45+ macrophages leading to HIF1-α stabilization, suggesting an E. faecalis-driven Warburg-like effect that favors persistence during wound infection. To further investigate the mechanism of E. faecalis persistence in wounds, we examined its ability to survive within keratinocytes which are the major cell type in the epidermis. We discovered that E. faecalis can be taken up by keratinocytes in a process that is dependent on actin polymerization and PI3K signaling, where they can survive for up to 72 hours. Within keratinocytes, E. faecalis can replicate within spacious Lamp1+ compartments and subsequently escape this compartment to re-infect nearby cells. We have determined that E. faecalis phospholipase C and sortase-assembled pili contribute to intracellular trafficking. Taken together, this work shows that the classical extracellular pathogen, E. faecalis has an intracellular lifecycle, where internalized bacteria can survive, replicate and escape from the infected cell, and which contributes to the persistence and non-healing state of infected wounds.