The objective of this study was to measure indicators of oxidative stress and serum concentrations of acute phase proteins of dairy cows (n = 38) fed a Saccharomyces cerevisiae fermentation product (SCFP, NutriTek, Diamond V, Cedar Rapids, IA) during the calving transition period. Four weeks before calving cows were fed a common close up diet consisting of 13% starch with or without SCFP. For 3 weeks after calving, cows were fed high or low starch (HS vs. LS; 27 and 21%, respectively) diets with (SCFP) or without SCFP (CON). Animals were assigned to one of 4 treatments (CON+HS, CON+LS, SCFP+HS, SCFP+LS) balanced for BCS and parity in a randomized block design. Data were analyzed with the Fit Model procedure of JMP. There was no interaction between starch content and SCFP treatments. The dietary starch content did not affect serum concentrations of haptoglobin (Hp) and serum-amyloid A (SAA), or plasma concentrations of total-antioxidant capacity (TAOC), malondialdehyde (MDA), and reactive oxygen metabolites, but SCFP feeding decreased serum Hp concentration on d 7 after calving compared with CON (0.26 vs. 0.62 mg/mL; P = 0.03) indicating reduced post-calving inflammation. Serum-amyloid A did not differ between treatments although there was a positive relationship between Hp and SAA concentrations (r = 0.46; P < 0.01). Serum Hp concentration was positively correlated with plasma concentrations of free fatty acids (r = 0.14; P = 0.05) and β-hydroxybutyrate (r = 0.23; P < 0.01), but not to glucose (r = 0.02). Responses to SCFP in plasma concentrations of TAOC and MDA on d 21 after calving were affected by parity and the dietary starch content; feeding SCFP increased plasma MDA concentrations for primiparous cows fed the HS diets (20.8 vs. 15.2 μM; P = 0.03), and decreased plasma TAOC concentration for multiparous cows fed the LS diets (0.57 vs. 1.05 mM; P = 0.03). These data suggest that supplementation of a SCFP during the periparturient period may reduce inflammation after calving, but may not alleviate oxidative stress of dairy cows.