Intracellular Salmonella use a type III secretion system (TTSS) to translocate effector proteins across the phagosome membrane and thus promote vacuole membrane tubulation, resulting in intracellular survival. This work demonstrates that the effector SseJ binds the eukaryotic lipid transporter oxysterol binding protein 1 (OSBP1). SseJ directs OSBP1 to the endosomal compartment in a manner dependent on the TTSS located on Salmonella pathogenicity island 2 (SPI2). OSBP1 localization is mediated by both SseJ and another OSBP1-binding SPI2 translocated effector, the deubiquitinase SseL. Deletion of both SseJ and SseL reduced vacuolar integrity with increased bacteria released into the eukaryotic cytoplasm of epithelial cells, indicating that their combined activities are necessary for vacuole membrane stability. Cells knocked down for OSBP1 or deleted for the OSBP1-binding proteins VAPA/B also demonstrate loss of vacuole integrity, consistent with the hypothesis that OSBP1 recruitment is required for SPI2-mediated alterations that promote vacuolar integrity of salmonellae. Display omitted •Salmonella-secreted effector SseJ binds eukaryotic oxysterol binding protein 1•SseJ directs OSBP1 to the endosomal compartment•OSBP1 localization is mediated by both SseJ and another effector, SseL•Deletion of both SseJ and SseL increases bacterial release into the cytoplasm Kolodziejek et al. demonstrate that the Salmonella-secreted effector SseJ binds eukaryotic oxysterol binding protein 1 (OSBP1). SseJ directs OSBP1 to the endosome in concert with another effector, SseL. Deletion of both SseJ and SseL or OSBP1 knockdown increased bacterial cytoplasmic release, indicating that they are necessary for vacuolar stability.