OBJECTIVE To determine global and peripheral perfusion and oxygenation during anesthesia with equipotent doses of desflurane and propofol combined with a constant rate infusion of dexmedetomidine in horses. ANIMALS 6 warmblood horses. PROCEDURES Horses were premedicated with dexmedetomidine (3.5 μg•kg-1, IV). Anesthesia was induced with propofol or ketamine and maintained with desflurane or propofol (complete crossover design) combined with a constant rate infusion of dexmedetomidine (7 μg•kg-1 •h-1). Microperfusion and oxygenation of the rectal, oral, and esophageal mucosa were measured before and after sedation and during anesthesia at the minimal alveolar concentration and minimal infusion rate. Heart rate, mean arterial blood pressure, respiratory rate, cardiac output, and blood gas pressures were recorded during anesthesia. RESULTS Mean ± SD minimal alveolar concentration and minimal infusion rate were 2.6 ± 0.9% and 0.04 ± 0.01 mg•kg-1 •min-1, respectively. Peripheral microperfusion and oxygenation decreased significantly after dexmedetomidine administration for both treatments. Oxygenation returned to baseline values, whereas tissue microperfusion remained low during anesthesia. There were no differences in peripheral tissue microperfusion and oxygenation between treatments. Cardiac index was significantly higher and systemic vascular resistance was significantly lower for desflurane treatment than for propofol treatment. For the propofol treatment, Pao2 was significantly higher and there was less dead space and venous admixture than for the desflurane treatment. CONCLUSIONS AND CLINICAL RELEVANCE Dexmedetomidine decreased blood flow and oxygen saturation in peripheral tissues. Peripheral tissues were well oxygenated during anesthesia with desflurane and propofol combined with dexmedetomidine, whereas blood flow was reduced.