The aim of this study was to assess the effect of feeding a methionine (MET) or choline (CHO) source to dams on neonatal calf liver expression of genes related to methyl-donor pathways and energy metabolism. The experiment was conducted as a randomized complete block design with 2 × 2 factorial arrangement of MET (Smartamine M, Adisseo NA) and CHO (ReaShure, Balchem Inc.) level (with or without). Eighty Holstein calves born to cows receiving during the last ~4 wk of pregnancy MET (0.08% DMI; n = 20), CHO (60 g/d; n = 20), MIX (MET+CHO; n = 20) or control (CON; n = 20) were evaluated. Immediately after birth calves were separated from the dam, fed first colostrum, housed individually and fed a common milk replacer twice daily. Liver biopsies were harvested (n = 8/group) at 4 d of age for qPCR analysis. Data were analyzed using the MIXED procedure of SAS, with MET and CHO as a fixed effect, and also a methyl donor contrast effect was tested. Both methyl donors upregulated (P < 0.05) the expression of CBS, BHMT and MTR, while they downregulated (P < 0.001) SAHH expression, all of which are related to the one-carbon and methionine pathways and the transsulfuration pathway. MAT2A expression was downregulated (P = 0.05) in liver of MET calves and upregulated (P = 0.02) in CHO calves. Expression of PEMT, MAT1A and CHDH was not affected (P > 0.05) by maternal treatment. Glutathione metabolism enzyme (GCLC and GSR) expression also was not affected by maternal treatment (P > 0.05). Regarding taurine metabolism, maternal supplementation with CHO upregulated (P = 0.05) CSAD hepatic expression, but CDO expression was not affected (P > 0.05). Expression of genes related to carbohydrate metabolism and hepatokines (PC, PCK1, SLC2A2 and FGF21) was not affected by maternal diet (P > 0.05). However, the glucocorticoid receptor was upregulated (P = 0.06) by maternal MET (P = 0.08) or CHO (P = 0.09) but not by their combination (MIX, P = 0.25). Overall, the data suggest that maternal feeding with methyl donors during the last ~4 wk of gestation elicited changes in neonatal calf hepatic gene expression and the response is different according to the methyl donor source.