Mate is a xanthine-containing beverage, which is prepared as an infusion of the dried and ground leaves of Ilex paraguariensis St. Hil. (Aquifoliacea). Previous reports have shown that Ilex paraguariensis has the highest levels of caffeine and theobromine when compared to other Ilex species. Furthermore, mate is able to interfere in the circulatory system, acting as a diuretic and hypotensive agent. Many processes of vascular injury result in the release of adenine nucleotides, which exert a variety of effects. Nucleoside 5′ tri- and diphosphates may be hydrolyzed by members of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) family. The synchronic action of a NTPDase and a 5′-nucleotidase promotes the catabolism of ATP to adenosine, which is able to control the extracellular nucleotides/nucleosides ratio. The chronic ingestion of aqueous extract of Ilex paraguariensis by rats during 15 days significantly decreased ATP (55%), ADP (50%) and AMP (40%) hydrolysis in blood serum. These results suggest changes in the balance of purine levels induced by Ilex paraguariensis ingestion. Considering the potential effects of Ilex paraguariensis in the circulatory system, these results may be relevant since NTPDases are a novel drug target for the treatment of cardiovascular diseases.