Pressure sores (PS) affecting muscles are severe injuries associated with ischemia, impaired metabolic activity, excessive tissue deformation and insufficient lymph drainage caused by prolonged and intensive mechanical loads. We hypothesize that mechanical properties of muscle tissue change as a result of exposure to prolonged and intensive loads. Such changes may affect the distribution of stresses in soft tissues under bony prominences and potentially, expose additional uninjured regions of muscle tissue to intensified stresses. In this study, we characterized changes in tangent elastic moduli (E_t) and strain energy densities (SED) of rat gracilis muscles exposed to pressure in vivo (11.5, 35 or 70 KPa for 2, 4 or 6 hours), and incorporated the abnormal properties that were measured in finite element (FE) models of the head, shoulders, pelvis and heels of a recumbent patient. Using in vitro uniaxial tension testing, we found that Et of muscles exposed to 35 and 70 KPa were 1.6-fold those of controls (p<0.05, for strains 5%) and SED were 1.4-fold those of controls (p<0.05, for strains 5%). Histological (PTAH) evaluation showed that this stiffening accompanied extensive necrotic damage. Incorporating these effects into the FE models we were able to show that the increased muscle stiffness in widening regions results in elevated tissue stresses which exacerbate the potential for tissue necrosis. Interfacial pressures could not predict deep muscle (e.g. longissimus or gluteus) stresses and injuring conditions. We conclude that information on internal muscle stresses is required to establish new criteria for PS prevention.