Sleep alters respiratory mechanics and gas exchange, which can adversely affect arterial oxygenation. Whether sleep affects oxygenation in hepatopulmonary syndrome is unknown. The aim of this study was to assess oxygen desaturation during sleep in hepatopulmonary syndrome. Twenty adults with cirrhosis including 10 controls and 10 patients with hepatopulmonary syndrome underwent home pulse-oximetry during sleep. Subjects at high risk for obstructive sleep apnea were excluded through the Berlin questionnaire. Subjects who spent more than 10% of total sleep time with arterial oxygen saturation < 90% were classified as sleep-time oxygen desaturators. Sleep-time desaturation was correlated with clinical variables. The results showed that 7 of 10 hepatopulmonary syndrome subjects and none of the 10 controls had sleep-time oxygen desaturation. The median percentage of total sleep time with arterial oxygen saturation < 90% was significantly higher in hepatopulmonary syndrome subjects than in controls (medians 25% versus 0%, P β«Ψβ¬ 0.005). Hepatopulmonary syndrome subjects had significantly lower wake-time arterial oxygen saturation level (median, 97% versus 95%; P β«Ψβ¬ 0.003) and mean sleep-time arterial oxygen saturation level (median, 96% versus 91%; P β«Ψβ¬ 0.0008) than did the controls. Sleep-time desaturation directly correlated with alveolar-arterial oxygen gradient (P β«Ψβ¬ 0.0007) and inversely correlated with wake-time arterial oxygen tension (P β«Ψβ¬ 0.0007) and oxygen saturation (P < 0.0001). Conclusion: Oxygen desaturation occurred during sleep in 70% of hepatopulmonary syndrome subjects, the degree of which correlated with the severity of hepatopulmonary syndrome. Marked hypoxemia during sleep may occur in hepatopulmonary syndrome patients who, according to wake-time oxygen values, have only mild to moderate hypoxemia.