Since decreased nutrient flow has been proposed as the cause of hepatocellular dysfunction during sepsis, we studied hepatic Na+ and K+ balance in rats with sepsis to determine if these changes were consistent with ischemia-induced hepatocellular damage. Sepsis was produced in rats by cecal ligation and puncture (CLP). Seventeen to 19 hours following CLP, the rats were found to have late sepsis but not septic shock. At this time, either hepatic and RBC Na+ and K+ were determined in vivo, or the livers were isolated and perfused with Krebsbicarbonate buffer for 30 minutes prior to determining hepatic tissue Na+ and K+ levels. In contrast to previous reports of hemorrhagic shock and following hepatic ischemia, there was a significant increase in hepatic K+ in vivo and after 30 minutes of isolated perfusion in vitro. No significant changes were detected in RBC Na+ or K+. Thus, although decreased hepatic nutrient flow may develop during sepsis, hypoperfusion is not the cause of hepatocellular dysfunction. © 1984, American Medical Association. All rights reserved.