This randomized, controlled, crossover study evaluated the effect of continuous positive airway pressure (CPAP) breathing on hepatic blood flow (HBF) and cardiac output in 10 healthy male subjects. A CPAP mask was placed on the face and the subject breathed at either CPAP 12.5 cm H2O or ambient airway pressure. The estimated HBF was calculated as the ratio of indocyanine green plasma clearance to one minus the hematocrit. Cardiac output was measured with Doppler ultrasound. CPAP caused HBF to decrease in 8 of 10 subjects (14.1% +/- 15.3%, mean +/- SD, p = 0.033) and cardiac index (CI) to decrease in all subjects (14.1% +/- 5.7%, p = 0.0001). Stroke volume and respiratory rate were significantly decreased; heart rate was unchanged. These results indicate that CPAP at 12.5 cm H2O causes a small, but significant decrease in both HBF and CI.