The aim of this study was to analyze the response of dry goat liver to sub-acute ruminal acidosis induced by a highly concentrated diet. Non-pregnant, non-lactating female Poll-goats (N = 12) were randomly assigned to either a high-concentrate (HG) or a low-concentrate (LG) diet. Low rumen pH was successfully induced with HG (more than 3 h with rumen pH < 5.8). The plasma lipopolysaccharide concentration was significantly decreased in the HG compared with LG group (P < 0.05). Proteomic analysis showed that aldehyde dehydrogenases and microsomal glutathione S-transferase was downregulated in the HG group, whereas aldo-keto reductase was upregulated compared in the LG group. The abundance of mRNA for these proteins were also correspondingly increased (aldehyde dehydrogenases and microsomal glutathione-S-transferase) or decreased (aldo-keto reductase) in the HG group. Malondialdehyde content in the liver was decreased in the HG group compared to the LG group. These data indicate that the expression of hepatic proteins alters the regulation of endogenous lipopolysaccharide during low rumen pH in dry dairy goats. In particular, the protective effect of the liver may occur through inhibition of aldehyde and/or peroxide formation.