Objective To investigate the effect of cardiac output and liver blood flow on propofol concentrations in critically ill patients in the intensive care unit. Methods Five medical/surgical critically ill patients were enrolled in this preliminary study. Liver blood flow was measured using sorbitol. The cardiac output was measured by bolus thermodilution. NONMEM ver. V was applied for propofol pharmacokinetic analysis. Results The clearance of propofol was positively influenced by the liver blood flow (P < 0.005), whereas no significant correlation between cardiac output and propofol clearance was found. A correlation between liver blood flow and cardiac output or cardiac index could not be assumed in this patient group. Conclusions Liver blood flow is a more predictive indicator than cardiac output for propofol clearance in critically ill patients when the techniques of hepatic sorbitol clearance and bolus thermodilution, respectively, are used. Further study is needed to determine the role played by liver blood flow and cardiac output on the pharmacokinetics of highly extracted drugs in order to reduce the observed high interindividual variabilities in response in critically ill patients.