An in silico approach was applied to investigate the possible role of microRNAs (miRNA) in the liver transcriptome response to prepartum body condition score (BCS) and feeding management in the weeks before calving. Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to 1 of 4 treatment groups in a 2 × 2 factorial design: 2 prepartum BCS categories [4.0 (thin) and 5.0 (optimal); 10-point scale], and 2 levels of energy intake during the 3 wk preceding calving (75% and 125% of estimated requirements). Liver tissue was harvested by biopsy at −7 and 7 d relative to calving and subsequent RNA was hybridized to the Agilent 44K Bovine V2 Microarray chip. A MIXED model with repeated measures was fitted to the normalized log₂-tranformed adjusted ratios using Proc MIXED. The transcriptome profile for the comparisons BCS 4 125vs75 and BCS 5 125vs75 was used to predict miRNA activity through 3 approaches: Wilcoxon rank test, ranked ratio, and mean absolute expression (results were overlapped to find common predicted miRNA). The analysis was performed on a list of miRNA families and their predicted target genes for B. taurus downloaded from the Microcosm targets website (v. 5.0). The dynamic impact approach was used for pathway analysis on the target differentially expressed genes (fold change < −1.5 or >1.5, P < 0.05) of the predicted miRNA at each time point. For BCS 4 there were 9 and 7 miRNA (pre- and postpartum, respectively) predicted to be involved in the response to prepartal nutrition. Their activity was related to cell proliferation and immune signaling. Postpartum, they also involved pyruvate, nitrogen, glutathione, and glycan metabolism. For BCS 5 only 2 (pre-) and 1 (postpartum) miRNA were common to the 3 approaches, with ubiquitin-mediated proteolysis affected prepartum, and mineral absorption, bile secretion, and tryptophan metabolism potentially regulated by miRNA postpartum. Overall, miRNA seem to be involved in the response to prepartum BCS and nutrition, particularly in thinner cows.