Several hypotheses exist for the etiology of decubitus ulcers, with external pressures exceeding internal capillary pressures over bony prominences claimed to be the major factor. This investigation evaluated the mechanical changes that occurred in human skin as a result of its exposure to static versus cyclic normal pressures of the magnitudes earlier recorded for the heels of human subjects on various support surfaces. The skin was characterized through uniaxial tensile testing. Static pressure alone altered the tissue's mechanical properties more than dynamic pressure cycles. Tissue subjected to pressure prior to uniaxial tensile testing always was less stiff than control tissue. Damage to the initially randomly oriented tissue collagen fiber bundles in the fibrous matrix, which may occur as a result of sustained compression, may be the cause of a decrease in stiffness of tissue subjected to prior pressure loading. This is the first report of compressive-pre-load-induced strain softening (Mullins effect) of a biological material.