Mate (Ilex paraguariensis A. St.-Hil) is a native species of South America used to prepare traditional beverages. Recently a possible effect of its infusion on oxidative stress found in dyslipidemias has been reported. The main compounds related to these activities are phenolic compounds derived from chlorogenic acid. This study aimed to determine the anticholesteremic effect of the hydroethanolic extract (HEIP) and its n-butanolic fraction (n-BFIP), with standardized content of phenolic compounds derived from chlorogenic acid, in rats treated with high-fat diet (HFD). The contents of these compounds in the ethanol extract and n-butanol fraction were respectively two and three times higher than in traditional infusion with predominance of dicaffeoylquinic derivatives. The extracts were able to reduce serum triglycerides and cholesterol and decrease the atherogenic index in treated animals. These results support a potential effect of the mate extract in cardiovascular disease.