This study conducted to investigate potential differences in the activity of genes involved in volatile fatty acid (VFA) absorption, pH regulation, and energy metabolism in epithelial cells of forestomach administered either endophyte-infected (E+; 4.45 mg ergovaline/kg) or endophyte-free (E−) tall fescue seed. Twelve steers [body weight (BW) = 547 ± 9 kg] were fed alfalfa cubes at 1.5 × NEm and dosed 1 kg of ground tall fescue seed daily via rumen cannula for 21 days. On day 22, steers were slaughtered, and tissue samples were collected from the rumen, reticulum, omasum, and abomasum. Gene expression analysis revealed that monocarboxylate transporters (MCT), isoform 1 and MCT4 expression levels were significantly lower (p<0.05) in the rumen epithelium of steers dosed with E+ seed, while MCT2 expression remained unchanged. Similarly, sodium hydrogen exchanger (NHE), isoform 2 expression was significantly reduced (p<0.05) in the E+ seed, whereas NHE1 and NHE3 were unaffected by the seed treatment. Additionally, expression levels of down regulated in adenoma (DRA) and anion exchanger (AE), isoform 2 were lower (p<0.05) in the rumen epithelium of E+ steers, while putative anion transporter 1, sodium bicarbonate cotransporter, isoform 1, 3-hydroxy 3-methylglutaryl coenzyme A synthase, isoform 2, and sodium potassium ATPase pump, isoform 1 expression levels were not influenced by the seed treatment. Notably, gene expression in the reticulum, omasum, and abomasum epithelia was unaffected (p>0.05) by seed exposure. These findings suggest that endophyte-infected tall fescue seed may impair ruminal VFA absorption in its dissociated state (pH > 5.8) by downregulating MCT1 and MCT4, along with suppressing NHE2, DRA, and AE2. Therefore, this mechanism may partially explain the reduced weight gain associated with fescue toxicosis in cattle.