The objective of this study was to compare blood profiles of intact and mastectomized periparturient cows to discriminate those metabolic changes associated with the act of parturition from the metabolic changes caused by lactation. Mastectomized and intact cows had similar increases in plasma estrogens and cortisol concentrations around the time of calving. Mastectomy eliminated hypocalcemia and the rise in 9,13-di-cis retinoic acid observed in intact cows. Mastectomy reduced but did not eliminate decreases in plasma phosphorus, alpha-tocopherol, and beta-carotene associated with parturition in intact cows, suggesting the mammary gland is not the sole factor affecting plasma concentrations of these compounds. Dry matter intake was similar in both groups before calving. The day of calving, dry matter intake was lower in intact cows than in mastectomized cows, but after calving the mastectomized cows exhibited a pronounced decline in feed intake. Plasma nonesterified fatty acid (NEFA) concentrations rose rapidly in intact cows at calving and did not return to baseline level for > 10 d. In contrast, NEFA concentrations in mastectomized cow plasma rose moderately at calving and returned to baseline level 1 to 2 d after calving. This study provides evidence that hypocalcemia in the cow is solely a result of the calcium drain of lactation. The act of parturition affects blood phosphorus, dry matter intake, and NEFA concentration independent of the effect of lactation.