Features of biophysical properties in blood cells from the elderly under mechanical stress applied in vitro have been studied. This stress was reported to trigger the signaling pathway engaged by purinergic receptor activation. The stiffness of the cell surfaces of red blood cells, granulocytes, lymphocytes, and platelets decreased, and the surface potential became more positive. Our findings add to the knowledge of the effect of mechanical deformation on leukocytes and platelets, which are the key regulators of homeostatic processes in the microvasculature, and on red blood cells involved in the regulation of vascular tone in arterioles and tissue oxygenation in the elderly.