The aim was to evaluate the effect of supplementing pregnant cows with rumen-protected methionine (MET) on neonatal calf liver expression of genes related to energy/lipid metabolism, insulin signaling, growth hormone signaling and inflammation. Forty Holstein calves born to cows receiving during the last ~4 wk of pregnancy MET (Smartamine M, Adisseo NA; ~2.9:1 Lys:Met; n = 20) or control (CON, ~3.35:1 Lys:Met, n = 20) were used. Immediately after birth calves were separated from the dam, fed first colostrum within 6 h (3.8 L with minimum IgG concentration of 50 g/L), housed individually and fed a common milk replacer (25% CP, 17% fat) twice daily. Liver biopsies were harvested (n = 8/group) at 4, 14, 28 and 50 (~1 wk post-weaning) d of age. Data were analyzed as repeated measures using the MIXED procedure of SAS. No maternal diet effect (P > 0.05) was observed on calf growth (body weight and withers height) from birth through weaning. Expression of genes related to lipoprotein metabolism (APOB, MTTP) and growth hormone signaling (IGF1, GHR1A) were not (P > 0.05) affected by maternal diet, but increased in expression over time (P < 0.05). PCK1 and FBP1 expression was greater (P = 0.05 and 0.02) in MET calves and increased (P < 0.001) over time in both groups. PC expression, however, was lower (P = 0.007) in MET calves and decreased (P < 0.001) over time in both groups. Lower (P = 0.001) ACOX1 expression was observed in MET, while CPT1A was greater (P < 0.001). The insulin-signaling related genes AKT2 and SLC2A2 had greater (P < 0.01) expression in MET calves. Except for FOXO1 and SLC2A2, all other genes evaluated in this pathway (INSR, IRS1, AKT2, SREBF1) increased (P < 0.05) expression over time regardless of maternal diet. MET calves had higher NFKB (P = 0.009) and SOD2 (P < 0.001) expression, and also a trend (P = 0.08) for higher SOD1. Overall, the data suggest that maternal supplementation with MET during the last ~4 wk of gestation elicited changes in calf hepatic gene expression and, as such, might have led to functional differences in improving neonatal energy metabolism.