Sepsis alters energy production and utilization by the liver. Changes in both metabolic pathways that produce substrate (gluconeogenesis or ketogenesis) for organism-wide consumption or provide an alternative source of fuel for the liver (β-oxidation and amino acid metabolism) have been identified. In this study, we test the hypothesis that these changes occur via an alteration in the transcription of key enzymes within each pathway. Male Sprague-Dawley rats were made septic using cecal ligation and single puncture with sham operated animals serving as controls. Hepatic tissue was harvested at 0, 3, 6, 16, 24, 48, and 72 h and either total RNA or hepatic nuclei were isolated. Using Northern blot hybridization analysis, the steady-state levels of phosphoeno/pyruvate carboxykinase, glucose-6-phosphatase, carnitine palmitoyl transferase II, acetyl coenzyme A-acyltransferase, and ornithine transcarbamylase mRNAs were determined. Using transcript elongation analysis, the rate of transcription of each gene was investigated. Relative to control, steady-state mRNA levels and rates of transcription for all five genes were decreased by ligation and single puncture. These decreases were persistent, with only partial recovery of either mRNA levels or transcription rates at 72 h. These findings could explain in part the long-term alterations in gluconeogenesis, β-oxidation, and ureagenesis observed in sepsis. More importantly, decreased transcription of certain genes seems to be a characteristic of sepsis-induced changes in hepatic function. Understanding the mechanisms that decrease transcription also may explain other aspects of sepsis in the liver and other organ systems.