Background. Thoracic surgery often requires one-lung ventilation. During one-lung ventilation, arterial oxygenation depends on the distribution of lung perfusion between the ventilated and the non-ventilated lung. Objectives. This study investigates the effects of sevoflurane and propofol on pulmonary perfusion and arterial oxygenation during one-lung ventilation in living animals at comparable mean arterial pressures. Material and Methods. A prospective study with a crossover design involving 12 pigs was carried out at the Institute for Experimental Animals, University of Jena, Germany. After the induction of anesthesia, a left-sided double-lumen tube was inserted via tracheotomy. One-lung ventilation was started with 1.0 FiO2, and anesthesia was continued with either propofol or sevoflurane (2.6% end-tidal concentration). After stabilization, the hemodynamic parameters and oxygenation were recorded, and differential lung perfusion was measured with colored microspheres. Then the anesthetic was changed and, after another stabilization period, the measurements were repeated. Results. The arterial oxygenation, mixed venous pO2, non-ventilated lung perfusion and shunt fraction were comparable during one-lung ventilation with both agents, whereas cardiac output was reduced during sevoflurane anesthesia (p < 0.05). Conclusions. In a clinically relevant animal model of one-lung ventilation, sevoflurane, as compared with propofol, did not increase the non-ventilated lung perfusion and shunt fraction and did not worsen arterial oxygenation (Adv Clin Exp Med 2011, 20, 3, 249–253).