Sirtuins (Sirt) are NAD-dependent deacetylases that are activated by the antioxidants resveratrol (RSV) and lipoic acid (LA). The objective of this study was to determine in bovine liver and muscle slice cultures the effect of RSV and LA treatment on the expresssion of Sirt1, Sirt3, peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A), and the forkhead box O transcription factors FoxO1 and FoxO3 as well as other factors involved in glucose and lipid metabolism and related to Sirt activity. Tissue slices from crossbred bulls were treated during 60 min with 40 or 80 μ RSV and 30, 100, 300, or 1,000 μ LA under restricted conditions (Krebs-Ringer buffer without nutrients) and fed conditions (2.5 m propionate in combination with 1 n glucagon) for liver slices or with 0.01 μ epinephrine for muscle slices. Quantitative real-time PCR was used to analyze the expression of the mRNA for the genes studied and western blot analysis for the expression of the protein for Sirt1. Our results show that the expression of the mRNA for Sirt1 was enhanced by RSV in liver under restriction ( ≤ 0.0112) and by LA in muscle, more under restriction ( ≤ 0.0121) than after epinephrine administration ( < 0.0001). Sirt3 is affected in a dose-dependent manner by both compounds in both tissues and under both metabolic conditions ( ≤ 0.0452). The expression of the protein for Sirt1 was increased by LA in both tissues under restricted conditions ( = 0.0026 and = 0.0201, respectively) but in liver also in fed conditions ( = 0.0016). Genes involved in the antioxidant response were upregulated in both tissues. These results indicate that bovine Sirt respond differently to RSV and LA stimulation than monogastric Sirt do and that gluconeogenesis in ruminants is not related to Sirt to the same degree as in monogastric species. However, these results provide information about the possible role of Sirt in ruminant metabolism.