Purpose Cerebral desaturation occurs frequently in patients undergoing one-lung ventilation for thoracic surgery. The mechanism of this desaturation is unclear regarding its etiology. The objective of this study was to investigate whether or not decreases in cerebral oxygen saturation associated with one-lung ventilation were a consequence of decreased cardiac output. Methods A blinded observational study was conducted in 23 patients undergoing one-lung ventilation with thoracic surgery. Eighteen patients completed the study. Cerebral oxygen saturation was monitored using near-infrared spectroscopy (FORE-SIGHT Ò monitor). Invasive blood pressure was monitored and hemodynamic variables were interrogated using the FloTrac Ò system. Anesthesia was maintained with sevoflurane with a F I O 2 of 1.0. Post-hoc analysis involved a comparison between baseline and integrated changes in cerebral saturation, heart rate, stroke index, cardiac index, and stroke volume variability. Results All patients showed cerebral desaturation from a baseline of two-lung ventilation in the lateral decubitus position following institution of one-lung ventilation. The cardiac index was stable at these times, but with one-lung ventilation, the heart rate decreased and the stroke index increased to maintain a stable product. The integral of heart rate 9 time was inversely correlated with the integral of cerebral desaturation 9 time (linear regression analysis; P = 0.02; (df) = 16)). Conclusions Cerebral oxygen desaturation was universal during one-lung ventilation in this study. There was no correlation between cerebral desaturation and cardiac output or other hemodynamic variables.