The present study investigates the effect of yeast (Saccharomyces cerivisea) autolysate (YA) on digestibility, rumen fermentation specially rumen microflora, blood parameters and growth of both suckling and growing buffalo calves Twelve suckling calves with an average body weight of 35.5±0.5 kg were randomly divided to three groups (4 calves each). The experimental period was divided into two phases, the first phase lasted 90 days after calving whereas, the second phase lasted 150 days started by weaning calves (90 days of age). In the first phase, animals in all groups suckled whole milk (WM) twice daily in addition to starter and berseem. In the second phase, animals were fed the basal rations composed of concentrate feed mixture (CFM), rice straw (RS) and berseem (Br). The experimental rations were R1: WM (control), R2: WM+ 5 ml of YA/h/d (5ml equal 1 gram of YA) and R3: WM+7.5 ml of YA, in the first phase. While during the second phase, the rations were R1: basal ration (control), R2: basal ration +35 of YA and R3: basal ration +50 ml YA. The results showed that addition of YA increased (P<0.05) digestibility of CP and CF, but it had no significant effect for other nutrients. The nutritive value as TDN was significantly (P<0.05) increased by addition of YA. Blood parameters (GPT, GOT and creatinine) and rumen fermentation were not affected by addition of YA except rumen pH which was significantly (P<0.05) higher for animal fed rations contained YA compared to the control. In the first phase, weaning body weight was significantly (P<0.05) increased by YA addition, on other hand, final body weight and ADG were not affected in the second phase. Feed conversion, daily profit, relative feed cost and relative daily profit were improved by treatment. Bacteriological examination revealed that the addition of YA decreased total aerobic bacterial count but it significantly (P<0.05) increased Lactobacillus count in feces of treated suckling calves with YA compared with control. Also, Lactobacillus count was significantly increased while; total number of aerobic bacteria was decreased in rumen fluid of growing calves by addition of YA. In vitro sensitivity of YA on the isolated three E. coli strains from control group revealed that there is strain variation in this respect as one strain (O27) showed the lowest count after treatment with yeast (less than 10 CFU) and the other two strains (O127 and un- typed strain). Results obtained revealed that using YA as feed additives for suckling and growing buffaloe calves tended to increase average daily gain, improved feed conversion  and get more profit relative to feed cost or a relative daily profit. Moreover, addition YA appeared to decrease of aerobic bacteria with increase Lactobacillus.