Availability of platelets for transfusions is limited by a five day maximum storage time which may be caused by a decline in platelet mitochondrial energy metabolism. The metabolic profile of freshly prepared platelets may also reflect acute stress, e.g., that associated with cardiopulmonary bypass surgery, or chronic stress, e.g., that associated with severe depression and fatigue. In preparation for measurements of oxygen consumption by fresh and stored platelets, experiments were performed to optimize platelet isolation and the conditions used during cell respirometry. Preliminary results indicate that maximal platelet respiration declines within 6 days of normal storage and is associated with an increase in apoptosis. No differences in platelet respiration were observed following bypass surgery; however, alterations in metabolic efficiency were observed in two post-stroke patients suffering from depression and fatigue. Platelet respirometry could lead to improved storage times and to its use as a biomarker of bioenergetic dysfunction.