Vasoactive agents are used in critical care to optimize circulatory function, but their effects on renal tissue oxygenation in the absence of anesthesia remain largely unknown. Therefore, we assessed the effects of multiple vasoactive agents on regional kidney oxygenation in awake sheep. Sheep were surgically instrumented with pulmonary and renal artery flow probes, and combination fiber-optic probes, in the renal cortex and medulla, comprising a fluorescence optode to measure tissue PO₂ and a laser-Doppler probe to assess tissue perfusion. Carotid arterial and renal venous cannulae enabled measurement of arterial pressure and total renal oxygen delivery and consumption. Norepinephrine (0.1 or 0.8 µg/kg/min) dose-dependently reduced cortical and medullary laser Doppler flux (LDF) and PO₂ without significantly altering renal blood flow (RBF), or renal oxygen delivery or consumption. Angiotensin II (9.8±2.1 µg/h) reduced RBF by 21%, renal oxygen delivery by 28%, oxygen consumption by 18% and medullary PO₂ by 38%, but did not significantly alter cortical PO₂ or cortical or medullary LDF. Arginine vasopressin (3.3±0.5 µg/h) caused similar decreases in RBF and renal oxygen delivery, but did not significantly alter renal oxygen consumption or cortical or medullary LDF or PO₂. Captopril had no observable effects on cortical or medullary LDF or PO₂, at a dose that increased renal oxygen delivery by 24%, but did not significantly alter renal oxygen consumption. We conclude that vasoactive agents have diverse effects on regional kidney oxygenation in awake sheep that are not predictable from their effects on LDF, RBF or total renal oxygen delivery and consumption.