Deep tissue injury (DTI) is a severe form of pressure ulcer that originates at the bone-muscle interface. It results from mechanical damage and ischemic injury due to unrelieved pressure. Currently, there are no established clinical methods to detect the formation of DTI. Moreover, despite the many recommended methods for preventing pressure ulcers, none so far has significantly reduced the incidence of DTI. The goal of this study was to assess the effectiveness of a new electrical stimulation-based intervention, termed intermittent electrical stimulation (IES), in ameliorating the factors leading to DTI in individuals with compromised mobility and sensation. Specifically, we sought to determine whether IES-induced contractions in the gluteal muscles can 1) reduce pressure in tissue surrounding bony prominences susceptible to the development of DTI and 2) increase oxygenation in deep tissue. Experiments were conducted in individuals with spinal cord injury, and two paradigms of IES were utilized to induce contractions in the gluteus maximus muscles of the seated participants. Changes in surface pressure around the ischial tuberosities were assessed using a pressure-sensing mattress, and changes in deep tissue oxygenation were indirectly assessed using T₂*-weighted magnetic resonance imaging (MRI) techniques. Both IES paradigms significantly reduced pressure around the bony prominences in the buttocks by an average of 10-26% (P < 0.05). Furthermore, both IES paradigms induced significant increases in T₂* signal intensity (SI), indicating significant increases in tissue oxygenation, which were sustained for the duration of each 10-min trial (P < 0.05). Maximal increases in SI ranged from 2-3.3% (arbitrary units). Direct measurements of oxygenation in adult rats revealed that IES produces up to a 100% increase in tissue oxygenation. The results suggest that IES directly targets factors contributing to the development of DTI in people with reduced mobility and sensation and may therefore be an effective method for the prevention of deep pressure ulcers.