The objective of this study was to evaluate the impact of dietary starch level and monensin on the gene expression of some key enzymes related to hepatic gluconeogenesis and fatty acid metabolism during early lactation. Prior to parturition primiparous (primi; n = 16) and multiparous (multi; n = 33) Holstein cows were fed a common controlled energy close up diet with a daily topdress containing either 0 mg/d (Con) or 400 mg/d monensin (Mon). From d 1 to 21 postpartum, cows were fed a high starch (HS; 26.2% starch, 34.3% NDF, 22.7% ADF, 15.5% CP) or low starch (LS; 21.5% starch, 36.9% NDF, 25.2% ADF, 15.4% CP) diet with a daily topdress containing either Con or 450 mg/d Mon, continuing with prepartum topdress assignment. Liver biopsies were obtained from cows on d 7 postpartum for mRNA gene expression analysis. There was a tendency for a Mon × parity interaction for CPT1A (P = 0.13) such that primi cows fed Con had increased CPT1A expression compared with primi cows fed Mon, whereas multi cows fed Mon had increased CPT1A expression compared with multi cows fed Con. There was a tendency for a starch × Mon interaction on HMGCS2 expression (P = 0.12) such that cows fed LS and Mon tended to have decreased HMGCS2 expression relative to cows fed LS and Con. There were tendencies for Mon × parity interactions for PC (P = 0.13) and PCK1 (P = 0.09) such that multi cows fed Mon tended to have increased expression for both PC and PCK1. Correlation analysis was performed for all gene expression variables. Overall, relationships were similar in directionality and magnitude between cows fed HS and LS and Con and Mon. However, for cows fed Con there was a positive relationship between HMGCS2 and PC (r = 0.44; P = 0.02) and HMGCS2 and PCK1 (r = 0.78; P < 0.01), whereas cows fed Mon there was no relationship (r = 0.08; P = 0.72 and r = 0.34; P = 0.10, respectively). Overall, cows fed diets of different starch content in early lactation and monensin throughout the transition period had some alterations in hepatic expression of genes related to glucose and fatty acid metabolism.