We tested the hypothesis that lipopolysaccharide (LPS) leads to an imbalance between mesenteric oxygen delivery (o2) and gut metabolic demand for oxygen, even when cardiac index (CI) is within the normal range. Two groups of pentobarbital-anesthetized pigs (13 to 17 kg) were studied. The first group (LPS: n = 9) was infused over 20 min with Escherichia coli LPS (100 μg/kg) and resuscitated with normal saline (1.2 ml/kg·min). The second group (NS; n = 5) was not infused with LPS, but was resuscitated in the same way as the LPS group. Superior mesenteric arterial (SMA) blood flow and ileal intramucosal hydrogen ion concentration, [H+), were determined using a Doppler-shift probe and a tonometric catheter, respectively. Infusing LPS did not affect CI, although mean arterial pressure and systemic vascular resistance were significantly reduced. SMA flow and mesenteric o2 decreased significantly in the LPS group. Although mesenteric oxygen utilization was well preserved in both groups, ileal intramucosal [H+] was significantly higher in endotoxic animals. These data support the idea that mesenteric oxygen consumption is flow-limited in this clinically relevant porcine model of septic shock.