Liver metabolism and health in dairy cows during the periparturient period are affected by plane of nutrition pre-partum. Long-term adaptations in hepatic gene expression are important for complete understanding of liver function. We examined temporal gene expression profiles during the dry period and early lactation in liver of Holstein cows fed moderate dietary energy ad libitum or restricted during the entire dry period using a microarray consisting of 7,872 annotated cattle cDNA inserts and quantitative RT-PCR. We identified 85 genes with expression patterns that were affected by level of energy intake pre-partum over time. Restricted energy intake pre-partum resulted in more pronounced up-regulation of genes with key functions in hepatic fatty acid oxidation (CPT1A, ADIPOR2), gluconeogenesis (PC), and cholesterol synthesis (SC4MOL). Ad libitum feeding up-regulated a number of genes associated with liver triacylglycerol synthesis (DGAT1) and pro-inflammatory cytokines (TNFAIP3). Genomic responses to ad libitum feeding were accompanied by increased incorporation of palmitate to esterified products in vitro and increased liver triacylglycerol concentration in vivo. Overall, gene expression profiles due to plane of nutrition pre-partum partly explained differences in rates of liver palmitate metabolism, blood serum metabolite concentrations, and liver tissue triacylglycerol concentration. Our data show that moderate overfeeding of energy in the dry period, in the absence of obesity, results in transcriptional changes predisposing cows to fatty liver and perhaps compromising overall liver health during the periparturient period. In this context, controlled energy intake may confer an advantage to the cow by triggering hepatic molecular adaptations well ahead of parturition.