This study evaluated the effects of replacing corn with wheat on the lactation performance, ruminal fermentation, plasma metabolites and hormonal profiles of multiparous Holstein cows. Thirty-four multiparous cows were divided into two equal groups, based on parity, body condition score, and bodyweight. The basal diet was supplemented with 186 g/kg corn or wheat, and was offered from day -28 (±7) relative to the date of expected calving. After calving, all cows received the same diet for four weeks (day +28). The wheat diets increased (P <0.05) the body condition score in the peri-parturient period and caused greater changes in dry matter intake and bodyweight post-partum, with no differences in energy balance compared with the corn diets. Further, the wheat increased (P <0.05) the concentration of propionate in the rumen, thus reducing the ratio of acetate to propionate, and produced (P <0.05) more milk and milk protein, but had reduced levels of urea nitrogen in the milk and serum. Similarly, the wheat diets increased (P <0.05) the plasma concentrations of albumin and glucose, and reduced (P <0.05) triglycerides with no effect (P >0.10) post partum on insulin, cortisol, β-hydroxybutyric acid and aspartate aminotransferase. The replacement of corn with wheat increased (P <0.05) plasma calcium and reduced non-esterified fatty acids around calving (day 0±1) and post-partum (days 0 to +28), and reduced urinary pH during the last week relative to the date of expected calving.