This research communication addresses the hypothesis that the association of dietary vitamin E and Yerba Mate could help to prevent or decrease oxidation of milk enriched in unsaturated fatty acids (UFA). Four multiparous lactating Holstein cows were used in a 4 × 4 Latin square. Treatments were: (1) control diet with no Yerba Mate or vitamin E; (2) diet containing 375 IU/kg vitamin E; (3) diet containing 30 g/kg Yerba Mate; and (4) diet containing 375 IU/kg vitamin E and 30 g/kg Yerba Mate. To increase unsaturated fatty acids in milk, cows were fed 172 g/kg soybean seeds (on a dry matter basis). There was no interaction between vitamin E and Yerba Mate supplementation for milk antioxidant-related (polyphenols, reducing power, conjugated dienes, and TBARS) analyses. Milk reducing power was increased when cows were supplemented with Yerba Mate. Our results suggest that the association of dietary vitamin E and Yerba Mate does not help to prevent or decrease oxidation of milk in UFA.