The aim of this study was to examine the effects of ¿-lipoic acid (¿-LA) on liver mitochondrial bioenergetics and oxidative status for 8¿weeks in normal-healthy animals. A pair-fed group was included to differentiate between ¿-LA direct effects and those changes due to reduced food intake. ¿-LA decreased body weight gain, liver weight and insulin levels with no differences compared to its pair-fed group. ¿-LA significantly reduced energy efficiency, the activity of the electron transport chain complexes and induced a lower efficiency of oxidative phosphorylation with reduced ATP production. ¿-LA supplementation directly decreased plasma triglycerides (TGs), free fatty acids and ketone bodies levels. A significant reduction in hepatic TG content was also observed. A significant up-regulation of Cpt1a, Acadl and Sirt3, all ß-oxidation genes, along with a significant deacetylation of the forkhead transcription factor 3a (FOXO3A) was found in ¿-LA-treated animals. Thus, ¿-LA along with a standard chow diet has direct actions on lipid metabolism and liver by modulating mitochondrial function in normal-weight rats. These results should be taken into account when ¿-LA is administered or recommended to a healthy population.