As the dairy industry strives for efficiency, the cell metabolic rate increases, and the neutrophil function decreases. In the last 15 years, there has been a 28% increase in milk production (33.9 to 39.5 kg/cow/d), a 12% decline in total-tract feed passage rate (9.72 to 8.52 h) and a 1% decline in DM digestibility (66.02 to 65.12). This study examined the neutrophil function, productive and reproductive performance at 4 levels of cow vitamin supplementation (Low, AVG, high 25% and high 5% antioxidant/electron transport vitamin supplementation of vitamin A (A), vitamin E (E) and riboflavin (Ribo), measured as bacteria phagocytosis by neutrophils using a phagocytosis assay, Phagotest. The phagocytosis test was standardized to 100% phagocytosis, which indicates full neutrophil activity and no depression effect. A total of 756 Holstein cows were used in a randomized complete block design with cow as the experimental unit, treatment as the fixed effect, and block as the random effect (189 cows × 4 treatments). Cows were blocked by age, reproductive and productive performance, and were fed corn/corn silage diets formulated to meet or exceed current NRC recommendations. Treatments consisted of antioxidant vitamin supplementation (T1 = 80,000 IU A, 963 IU E and 0 mg Ribo, T2 = 120,000 IU A, 1444 IU E and 30 mf Ribo, T3 = 160,000 IU A, 1925 IU E and 60 mg Ribo, T4 = 224,000 IU A, 2650 IU E and 80 mg Ribo/H/D, respectively (adjusted to a 658 kg cow BW). Neutrophil phagocytosis (T1 = 65,T2 = 82, T3 = 95 and T4 = 100%, P = 0.04, respectively); bulk SCC (356, 285, 225 and 180 cell/mL, P = 0.03, respectively); incidence of clinical mastitis (35%, 20%, 14% and 10%, P = 0.02, respectively); number of days open (154, 132, 119 and 112, P = 0.03, respectively) and days to first service (97, 82 75 and 68, P = 0.03, respectively). Goodness-of-fit tests determined cow neutrophil and performance responses to vitamin supplementation. In conclusion, there was an excellent correlation between vitamin A, E and Riboflavin supplementation with neutrophil function (R² = 0.94), bulk somatic cell count (R² = −0.89), incidence of clinical mastitis (R² = −0.93) and number of days open (R² = −0.91).