Dopamine is widely used to improve systemic and hepatosplanchnic hemodynamics and oxygenation during sepsis. However, some studies have suggest that norepinephrine may have beneficial effects on regional blood flow and metabolism, whereas dopamine might have deleterious effects related to redistribution of blood flow away from the intestinal mucosa or by decreasing directly the cell redox state. In 12 vasoplegic septic patients, we compared the effects of norepinephrine and dopamine on systemic and hepatosplanchnic hemodynamics, oxygenation, and energy metabolism. Catecholamines were administered in a crossover randomized order to maintain mean arterial pressure (MAP) at 80 mmHg. Hepatosplanchnic blood flow (Qspl) was determined using a continuous infusion of indocyanine green dye. Despite a similar MAP, the cardiac index was higher with dopamine than with norepinephrine (6.3 [5.3-7.3] vs. 4.3 [3.8-4.9] L.min.m) (P <0.001). Qspl was similar with both catecholamines, but the ratio of Qspl to cardiac output was significantly lower with dopamine (23.9% [17.5-33.5]) than with norepinephrine (33.5% [25.8-37]) (P <0.05). Although global O2 delivery and O2 consumption were higher with dopamine (782 [707-859] vs. 553 [512-629] mL.min.m, P <0.001 and 164 [134-192] vs. 128 [111-149] mL.min.m, P <0.001, respectively), hepatosplanchnic O2 delivery and consumption were not different. Hepatic lactate uptake was lower (0.47 [0.3-0.89] vs. 1.01 [0.69-1.34] mmol.min) (P <0.01), and hepatic venous lactate-to-pyruvate ratio was higher (15.3 [7.6-21.1] vs. 11.2 [6.6-15.1], P <0.05) with dopamine than with norepinephrine. In vasoplegic septic patients, maintaining mean arterial pressure, hepatosplanchnic hemodynamics, and oxygen exchange with dopamine requires a consequent increased cardiac output, which is responsible for an increased global oxygen demand when compared with norepinephrine. In addition, dopamine impairs the hepatic energy balance. Its position as a preferential treatment compared with norepinephrine in this context may therefore be questionable.