Objective:To more clearly define the relationship between an oxygen flux test, oxygen supply dependency, and outcome in patients with sepsis, severe sepsis, or septic shock.Design:Prospective, interventional clinical trial.Setting:A teaching hospital general intensive care unit in London, UK.Patients:A total of 36 patients with sepsis, severe sepsis, or septic shock were studied during a 10-month period.Interventions:After resuscitation, patients were given an intravenous infusion of dobutamine at 10 μg/kg/min for 1 hr. Cardiac and respiratory variables were measured before the infusion and then while the infusion was in progress. Any patient who was able to increase his or her oxygen consumption by >15% was designated a responder to the test.Measurements and Main Results:Hemodynamic, oxygen transport, and lactate measurements were made at baseline and after 1 hr of the dobutamine infusion. All patients were then followed up until hospital discharge. Responders to this test had a hospital mortality of 14%, whereas nonresponders had a mortality of 91% (p< .01). The responders were characterized by being younger (p< .05), having higher Acute Physiology and Chronic Health Evaluation III scores (p< .05), and having a greater requirement for inotropic support (p< .05). After the test, the responders had significantly higher oxygen delivery (p< .01) and oxygen consumption (p< .05) than the nonresponders, as well as a significantly greater temperature increase as a result of the infusion (p< .05). The nonresponders were unable to increase either oxygen delivery or oxygen consumption to the dobutamine. This test was highly predictive of outcome (p< .0001). The identification of an increase in both oxygen delivery and oxygen consumption (oxygen supply dependency) was not associated with a poor outcome.Conclusion:A dobutamine oxygen flux test provides evidence of the intrinsic function of cells. The inability of these cells to increase oxidative metabolism during sepsis, as indicated by the dobutamine test, is associated with a high mortality.