The aim of the study reported in this Research Communication was to investigate the effect of a combined acetylmethionine, cyanocobalamin and α-lipoic acid treatment, on some metabolic parameters of early lactating high-yielding dairy cows. Thirty cows were randomly divided into two groups: experimental group (EG, n = 20) and control group (CG, n = 10). EG received 20 ml of treatment and CG received 20 ml of placebo. The treatments were administered for seven times every 2 d. Blood samples were collected from all cows at 3 time points: 10 ± 2, 30 ± 2 and 50 ± 2 d postpartum. Glucose, β-hydroxybutyrate (BHB), nonesterified fatty acids (NEFA), triglycerides, total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamiltransferase (GGT), total bilirubin (TB), conjugated bilirubin (CB), total proteins (TP), globulins, albumin and urea concentrations were determined. Two-way repeated measure analysis of variance was applied. Significant differences in the values of glucose, BHB, NEFA, triglycerides, TC, AST and urea were found between EG and CG. Moreover, the increased glucose, TC, ALT, GGT, TP and globulins, and the reduced BHB, NEFA, AST, triglycerides, TB, CB and urea concentrations were evident in both groups, but the changes were more pronounced in EG. Our findings indicate that our treatment positively influenced liver metabolism in high-yielding dairy cows.