Several studies demonstrated improved feed efficiency and beneficial effects on oxidative stress and immune function with supplementation of Saccharomyces cerevisiae fermentation product (XP, Diamond V, Cedar Rapids, IA). The objectives were to examine the effects of XP supplemented to high yielding dairy cows during the hot season on feed conversion ratio (FCR) and several markers of oxidative stress and inflammation. Mid-lactation cows (n = 42, 145 DIM and 50.5 kg milk/d) were divided into 2 groups, fed a standard Israeli ration, and supplemented for 10 wks with: Control (CTL), 100 g ground corn; or XP, a blend of 56 g XP + 100 g ground corn per cow per d. Blood samples were taken at d −1, 23, 49 and 56 of the study period. Rumen samples were taken at the 8th wk for pH, ammonia, and VFA measurements. Data were analyzed using the PROC MIXED model of SAS. Milk yields were similar, but milk components of fat (3.76 and 3.57%, respectively; P < 0.09) and protein (3.40 and 3.36%, respectively; P < 0.1) tended to be higher in the XP cows. The 4% fat-corrected milk (FCM) was 3.2% higher (P < 0.09) in the XP cows. Dry matter intake was similar between groups, and FCM FCR (DMI/FCM) tended to be lower (P < 0.1) in the XP fed group (690 and 710 g DMI/kg FCM, respectively). Rumen pH was higher in the CTL cows; butyrate concentration was higher in the XP cows, and the total VFA tended to be higher in the XP cows (P < 0.09). No differences were observed in tumor necrosis factor α (TNFα) concentrations in blood, but the inflammation marker interleukin-6 (IL6) and oxidative stress marker malondialdehyde (MDA) concentrations tended to be lower (P < 0.1) in the XP cows (29.0 and 63.4 pg/mL and 358.0 and 436.4 nM, respectively). In conclusion, supplementation of XP to dairy cows during the hot season tended to increase milk fat and protein content, and FCM yields and FCR. In addition, there were indication of beneficial effects of XP supplementation on oxidative stress and immune function.