Forty-eight Holstein cows were used to determine the effects of short-term oral drenches of propylene glycol (PG) and Ca-soaps of palm oil fatty acids (fat) on plasma concentrations of key metabolites, liver composition, and milk production during the first 3 wk of lactation. Treatments (2 x 2 factorial arrangement) given orally once daily for the first 3 d postpartum were water (control), 500 ml of PG, 454 g of fat, or 500 ml of PG plus 454 g of fat. All treatments were administered as a total volume of 1.9 L. Administration of PG decreased concentrations of nonesterified fatty acids (NEFA) in plasma during the first 7 d and the first 21 d postpartum and tended to decrease concentrations of beta-hydroxybutyrate during the first 7 d postpartum. Concentrations of insulin in plasma were not affected by treatment. Administration of either PG or fat increased plasma glucose and liver glycogen concentrations compared to the control or PG plus fat treatments. Concentrations of triglycerides in liver were not affected by treatment. Administration of PG did not affect dry matter intake or milk yield and composition during the first 3 wk postpartum; however, cows drenched with fat tended to have lower dry matter intake and milk yield during the first 3 wk of lactation. Short-term drenching of PG effectively decreased NEFA concentrations in plasma during early lactation; however, data do not support administration of fat via drench to early lactation cows and concurrent administration of dietary fat appears to blunt the metabolic response of cows to PG.