This experiment evaluated if strain type would induce differential response of lactating cows to Saccharomyces cerevisiae supplementation during Brazilian summer (THI >68 for 86.4% of time). Thirty Holsteins (169 ± 87 DIM) were milked 3x/d and individually fed on TMR for a 2-week covariate period and blocked by parity (1 vs. > 1) and milk yield before assignment to a treatment for 56 d. Treatments were: strains SC 47 or NCYC 996 (Phileo Lesaffre) or Control (CTL). Pre-planned contrasts were C1) CTL vs. SC 47 + NCYC 996 and C2) SC 47 vs. NCYC 996. Yeast products (10 g/cow/d) were mixed to a cup of ground corn and top dressed to the TMR in the morning. Viable and non-viable cells/g were: 1.00 × 10¹⁰ and 1.03 × 10¹⁰ for SC 47 and 1.76 × 10¹⁰ and 0.93 × 10¹⁰ for NCYC 996, respectively. Yeast products did not affect milk yield (35.8 kg/d, P ≥ 0.69), solids (1.048 protein, 0.953 fat, and 1.572 lactose. kg/d. P ≥ 0.37), and DMI (19.4 kg/d, P ≥ 0.62). Linear SCC scores were 4.94 for CTL (384,000 cells/mL), 4.17 for SC 47 (225,000 cells/mL), and 4.37 for NCYC 996 (258,000 cells/mL) (P < 0.01 for C1). Immune response was evaluated on d −1, 7, and 15 relative to vaccination with an inactivated rabies vaccine on d 35. Total leukocytes and interleukin-4 (IL-4) increased in all treatments in response to vaccination. Compared with SC 47, NCYC 996 tended to increase IL-4 on d −1 (P = 0.10 for C2) and reduced it on d 15 (P = 0.03 for C2). Gamma-interferon was not affected by treatments (P ≥ 0.19). Total-tract apparent digestibility of nutrients and the daily urinary allantoin excretion did not differ (P ≥ 0.20). Yeast increased ingestion time per day and per DMI and meal duration (P ≤ 0.02 for C1). Plasma niacin concentration on d 14 and 56 did not differ (P ≥ 0.62). Rectal temperature at 7 p.m. tended to be lower on NCYC 996 than SC 47 (39.4 vs. 39.1°C, P = 0.06 for C2), but respiratory frequency and sweating rate did not change (P ≥ 0.32). Plasma glucose concentration at 0, 2, 4, and 12 h post-feeding did not differ (P ≥ 0.22). Live yeast supplementation reduced milk SCC and affected immunity, but had no impact on animal performance, diet digestibility, and plasma niacin concentration and thermo-regulation.