Diets rich in n-3 polyunsaturated fatty acids (PUFA) improve the nutritional value of ruminant products but also increase the risk of lipoperoxidation in plasma and tissues. The relative effectiveness of dietary antioxidants such as vitamin E (vit E) given alone or with plant extracts rich in polyphenols (PERP) containing rosemary, grape, citrus, and marigold was investigated in the plasma of mid-lactation dairy cows given diets enriched in 18:3 n-3. For a 30-d period, the animals were given a maize silage-based diet (control group C, n = 6) or the same basal diet supplemented with extruded linseed rich in 18:3 n-3 [50 g of oil/kg of diet dry matter (DM); group L, n = 6], extruded linseed + vit E (375 international units/kg of diet DM; 7,500 IU/cow per day; group LE, n = 6), or extruded linseed + vit E + PERP (10 g/kg of diet DM; group LEP, n = 5). Plasma susceptibility to lipoperoxidation was evaluated using in vitro parameters of conjugated diene formation (lag phase and maximum oxidation rate). Plasma indicators of lipoperoxidation and antioxidant status were analyzed in the 4 experimental groups as well as the fatty acid (FA) composition of total plasma lipids. At d 30, group L significantly increased plasma cholesterol esters (+57%) and phospholipids (+35%) compared with group C. It also increased plasma n-3 PUFA (4.7-fold increase) to the detriment of n-6 PUFA (−30%), leading to a higher peroxidizability index (+20%). Plasma in vitro lipoperoxidation was higher in group L, rich in 18:3 n-3, than in group C. Vitamin E alone had no effect on lipoperoxidation, whereas vit E in association with PERP lowered lipoperoxidation by increasing the resistance time against peroxidation (+47%) and by decreasing the oxidation rate (−48%) compared with group L at d 30. Surprisingly, in vivo plasma lipoperoxidation estimated by the plasma level of the major lipoperoxidation product (malondialdehyde) was not significantly increased in group L. This study shows, for the first time, that PERP supplied in association with vit E were able to reduce lipoperoxidation in lactating cows given a diet rich in 18:3 n-3, thereby helping to protect cows against the deleterious consequences of lipoperoxidation and potentially ensuring antioxidant potential for 18:3 n-3–enriched dairy products.