We hypothesized that increasing the intestinal supply of Met could help alleviate inflammation and oxidative stress, and enhance neutrophil and monocyte function during the periparturient period and early lactation. Sixty multiparous Holstein cows were used in a block design and assigned to either a control or Met-supplemented (Mepron, Evonik Nutrition & Care GmbH, Germany) diet. Mepron was supplied from −28 to 60 d relative to parturition at a rate of 0.09% and 0.10% of DM during the prepartum and postpartum period, respectively. That rate ensured that the ratio of Lys to Met in the MP was close to 2.8:1. Blood samples from 15 clinically-healthy cows per treatment were collected at −30, −14, 1, 7, 21, 30 and 60 d relative to parturition and analyzed for biomarkers of energy balance, inflammation and oxidative stress. Neutrophil and monocyte function was measured at −10, 1, 7, 21 and 30 d relative to parturition. The statistical model included the random effect of block and fixed effect of treatment, time and interactions. The indicators of energy balance β-hydroxybutyrate, glucose and fatty acids were not affected by supply of Met. Among inflammation biomarkers measured, Met led to greater (P = 0.01; 38.1 vs 37.1 g/L) albumin (negative acute-phase protein) while ceruloplasmin (positive acute-phase protein), and myeloperoxidase were not affected by Met supply. The lower concentrations of reactive oxygen metabolites (P = 0.07; 15.2 vs 16.8 mg of H₂O/100 mL) and greater paraoxonase (P = 0.01; 94.8 vs 84.0 U/mL), β-carotene (P < 0.01; 0.24 vs 0.20 mg/100 mL), and tocopherol (P = 0.05; 5.38 vs 4.99 μg/mL) in Met cows indicated a state of reduced oxidative stress. Compared with control, Met enhanced in vitro neutrophil phagocytosis (P = 0.04; 59.4 vs 49.7%) and oxidative burst (P = 0.06; 53.1 vs 44.6%). However, monocyte function was not affected by Met. Overall, the results indicate that increasing Met supply by feeding ethyl-cellulose rumen-protected methionine is an effective approach to help mitigate oxidative stress as well as enhance neutrophil function during the peripartum period through the peak of lactation.