The objective was to evaluate the effect of live yeast (Saccharomyces cerevisiae Sc47-CNCM I-4407, 10¹⁰ cfu/g DM, Phileo Lesaffre Animal Care, France) and yeast derivatives (YP, 30 g/h/d) distributed to a total of 156 Holstein peripartum dairy cows (top dressing on TMR) on performances and health status. Cows were assigned randomly into 3 groups (C, YPP and YTP) according to their calving date: C received basal close-up (pre-partum) and early lactation (postpartum) diets; YPP received the basal diets suplemented with yeast-based products from −21d to 0d pre-partum; YTP received the basal diets supplemented with yeast-based products from −21d to +21d around calving. Milk yield was individually and daily measured. Milk composition was recorded every 2 weeks over the first 10 weeks of lactation. Somatic cells counts (SCC) linear score was determined using the 0 to 9 scale. Blood samples were collected −7d, 3d and 20d around calving for NEFA, BHB and IGF1 analysis. Milk production, quality and metabolic parameters were analyzed as repeated measures by using the general mixed model including fixed effects of treatment, week, parity, treatment x parity, treatment x week and random effect of cow. SCC linear score was significantly lower for YPP and YTP than C: 3.46 vs. 2.92 on average (P < 0.001). Blood NEFA and BHB contents were significantly lower for YPP (0.64 mmol/L and 0.35 mmol/L, respectively) than control (0.80 mmol/L and 0.45 mmol/L, respectively). Blood IGF1 content was significantly increased: 118.2 ng/mL and 98.5 ng/L with respect to YPP and C. Milk production over the first 15 weeks of lactation was significantly affected by treatments (P < 0.001): 35.8, 36.5 and 37.6 L/d for C, YPP and YTP, respectively. Milk yield of YPP tended to differ than C (P = 0.081) whereas C and YTP and YTP and YPP differed significantly. In conclusion, (i) YP given during the close-up period resulted in decreasing SCC in milk and alleviating negative energetic balance and (ii) in addition, supplementing YP during the entire transition period highly improve milk yield.