In vivo 31P- and 23Na-magnetic resonance spectroscopy was used to measure phosphorus metabolites, intracellular pH, cytosolic free Mg2+, and intracellular Na+ in the liver of rats 24 h after 40% total body surface area full-thickness burn injury. Studies were performed during infusion of thulium (III) 1,4,7,10-tetraazacyclododecane N,N',N",N"'-tetra(methylenephosphonate), which served as the Na+ shift agent. Compared with the sham-burn group, there was a significant increase in hepatic intracellular Na+ along with a decrease in intracellular pH and free Mg2+. The ratio of intra- to extra-cellular Na+ increased, indicating a decreased Na+ gradient that may determine the hepatic transmembrane potential difference. Hepatic beta-ATP/P(i) also significantly decreased, which suggests that either ATP utilization is significantly accelerated or ATP synthesis is inhibited after the thermal injury. Of the cations measured (Na+, Mg2+, H+), the change in intracellular Na+ was most dramatic. This study demonstrates that major burn injury may cause profound changes in hepatic bioenergetics and ionic metabolism 24 h after injury and that intracellular Na+ may be a sensitive indicator of hepatic dysfunction 24 h after injury. Because these animals tolerated the shift reagent, thulium (III) 1,4,7,10-tetraazacyclododecane N,N',N",N"'-tetra(methylenephosphonate), nuclear magnetic resonance spectroscopy may prove valuable in monitoring intracellular cations in the liver after major injury.