Abstract Saccharomyces cerevisiae fermentation product (SCFP) has been widely studied; however, its mode of action on high-concentrate diets has not been fully elucidated. This study evaluated the impact of SCFP on total tract digestibility, fecal excretions of N, P, Zn, and Cu, rumen fermentation, and plasma metabolome of finishing beef steers. Ruminally cannulated Holstein steers [n = 8; body weight (BW) = 580 ± 29.2 kg] were enrolled in a crossover design study with 25-d treatment periods and a 24-d washout period. Steers were fed ad libitum a finishing diet consisting of 20% corn silage and 80% concentrate (on DM basis). Steers were blocked based on initial BW and randomly assigned to two treatments in period 1 and switched to the other treatment in period 2. The treatments were CON (Control, basal diet only) and SCFP (basal diet top-dressed with 12 gּ steer-1ּ ּ d-1 SCFP, NaturSafe, Diamond V, Cedar Rapids, IA). Feed and fecal samples were collected during d 22 to 24 for determination of digestibility. Blood was collected before morning feeding on d 25. Plasma samples were analyzed for metabolome with liquid chromatography-mass spectrometry (LC-MS). Rumen fluid was collected via the rumen cannula at 0, 4, 8, and 12 h post-morning feeding on d 25 and analyzed for pH, volatile fatty acids (VFA), and NH3-N. Performance and ruminal fermentation characteristics data were analyzed using the GLIMMIX procedure of SAS 9.4. Metabolomic data analysis was conducted with Metaboanalyst 6.0. Supplementing steers with SCFP reduced DMI (10.6 vs. 11.4 kg/d, P = 0.05) without affecting (P > 0.05) average daily gain, feed efficiency, and digestibility of organic matter, crude protein, and neutral detergent fiber. Treatment did not affect (P > 0.10) fecal excretions of N, P, Cu, and Zn. Feeding SCFP increased ruminal pH (6.29 vs. 6.01, P = 0.01), numerically reduced concentrations of NH3-N (5.01 vs 6.25 mM, P = 0.16), and total VFA (96.8 vs. 102.5 mM, P = 0.15). SCFP also reduced the ruminal molar proportion of butyrate (11.2 vs. 12.8 molar %, P = 0.01) and tended to increase those of isobutyrate (1.03 vs. 0.90, molar %, P = 0.06) and isovalerate (2.62 vs. 2.29, molar %, P = 0.10). Supplementation of SCFP enriched (P ≤ 0.05) purine metabolism, amino sugar and nucleotide sugar metabolism, and lysine degradation pathways in the plasma. Additionally, tryptophan metabolism and pyrimidine metabolism pathways tended to be enriched (0.05 < P ≤ 0.10) by SCFP. Our findings indicate that feeding SCFP improved the ruminal pH of finishing cattle, which may be beneficial for preventing subacute ruminal acidosis in feedlot cattle. Additionally, SCFP enriched several important plasma nitrogen metabolism pathways, potentially associated with microbial nitrogen metabolism in the rumen, warranting further research.