The pathophysiology of sepsis-induced acute kidney injury remains poorly understood. As changes in renal perfusion and oxygenation have been shown, we aimed to study the short-term effects of endotoxemia on microvascular and interstitial oxygenation in the cortex and medulla, in conjunction with global and renal hemodynamics. In a 4-h rat model of endotoxemia, we simultaneously assessed renal artery blood flow and microvascular and interstitial oxygen tensions in the renal cortex and medulla using ultrasonic flowmetry, dual wavelength phosphorimetry, and tissue oxygen tension monitoring, respectively. Whereas medullary microvascular and interstitial oxygen tensions decreased promptly in line with macrovascular blood flow, changes in cortical oxygenation were only seen later on. During the entire experimental protocol, the gradient between microvascular PO 2 and tissue oxygen tension remained unchanged in both cortex and outer medulla. At study end, urine output was significantly decreased despite a maintained oxygen consumption rate. In this 4-h rat model of endotoxemia, total renal oxygen consumption and the gradient between microvascular PO 2 and tissue oxygen tension remained unaltered, despite falls in renal perfusion and oxygen delivery and urine output. Taken in conjunction with the decrease in urine output, our results could represent either a functional renal impairment or an adaptive response.