Resveratrol (RSV) and quercetin (QRC) modify energy metabolism and reduce cardiovascular risk factors included in the metabolic syndrome (MetS). These natural compounds upregulate and activate sirtuins (SIRTs), a family of NAD-dependent histone deacetylases. We analyzed the effect of two doses of a commercial combination of RSV and QRC on serum fatty acid composition and their regulation of SIRTs 1-3 and PPAR-γ expression in white adipose tissue. MetS was induced in Wistar rats by adding 30% sucrose to drinking water for five months. Rats were divided into control and two groups receiving the two different doses of RSV and QRC in drinking water daily for 4 weeks following the 5 months of sucrose treatment. Commercial kits were used to determine serum parameters and the expressions of SIRTs in WAT were analysed by western blot. In MetS rats body mass, central adiposity, insulin, triglycerides, non-HDL-C, leptin, adiponectin, monounsaturated fatty acids (MUFAs), and nonesterified fatty acids (NEFAs) were increased, while polyunsaturated fatty acids (PUFAs) and HDL-C were decreased. SIRT 1 and SIRT 2 were downregulated, while PPAR-γ was increased. RSV + QRC administration improved the serum health parameters modified by MetS and upregulate SIRT 1 and SIRT 2 expression in white abdominal tissue in MetS animals.