The aim of this study was to investigate the expression of genes encoding enzymes and other factors involved with carbohydrate and lipid metabolism in the liver of 2 genetic groups of dairy cows during the transition period. We analyzed the expression of glucose-6-phosphatase (G6PC), cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), methylmalonyl-CoA mutase (MUT), β-hydroxybutyrate dehydrogenase-2 (BDH2), acetyl-CoA carboxylase (ACC), carnitine palmitoyltransferase-2 (CPT2), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), glucose transporter-2 (SLC2A2), and the transcription factor peroxisome proliferator-activated receptor α (PPARA). Blood concentrations of glucose, nonesterified fatty acids, and β-hydroxybutyrate were also determined. Liver biopsies and blood samples were taken at d 15 prepartum and at d 6, 21, 36, 51, and 66 postpartum from Holsteins (n = 6) and F1 Holstein-Gir (n = 6) cows. Cows were kept under the same prepartum and postpartum management conditions. The results showed that the expression of G6PC, PEPCK-C, BDH2, ACC, CPT2, HMGCR, SLC2A2, and PPARA genes did not differ between genetic groups. Except for PEPCK-C, no interaction between genetic groups and the experimental period was observed. Within both groups of cows, G6PC and PEPCK-C gene expression decreased when comparing prepartum gene expression with 21 and 36 DIM, and increased in d 51 postpartum. MUT mRNA levels differed between the 2 genetic groups and displayed a significant increase after d 36 postpartum, whereas mRNA levels of HMGCR tended to increase when comparing d 21 and 36 to d 51 postpartum. Glucose concentrations also differed between genetic groups, being significantly higher in the plasma of F1 Holstein-Gir cows than in Holstein cows, but no differences were found within each group during the analysis period. β-Hydroxybutyrate and nonesterified fatty acid concentrations did not differ between genetic groups, but displayed increased levels from prepartum to d 6 and 21 postpartum. Our results indicated that expression in the liver of genes involved with glucose and fatty acid metabolism were similar in both groups of cows and significant differences were observed between the 2 groups in the expression of MUT, a gene involved in propionate metabolism.