Three experiments were conducted to investigate the effects of supplemental live yeast (SC) and mannan-oligosaccharides (MOS) and their combination on in vitro fermentation and in vivo metabolism and performance of ruminants. In experiment 1, a batch culture study was conducted in which supplementation of 1- no additive (CON), 2- monensin (MON, 5ppm/bactch), 3- mannan-oligosacharides (MOS, 10 -3 gr /batch), 4- SC (3.5 × 10 5 cfu/batch), and 5- MOS + SC was studied when added into inocula taken from high forage, and a high concentrate fed sheep. Alfalfa hay, derid corn silage and ground barley served as fermentation substrates. Incubation lasted for 24 hours. Additive did not affect ammonia nitrogen (NH3-N) concentration ( P 0.05). Supplementation of MON increased ( P 0.05), the SC decreased ( P 0.05) and the MOS did not change pH. Total gas production increased when SC or MOS was supplemented ( P 0.05). Results also showed that additive effects on in vitro parameters was differed based on inoculum source and substrate type. In the experiment 2, four ruminally fistulated sheep were used in a 4 × 4 Latin square design to study the effect of supplementation of diet with 1- CON , 2- MOS (1.2 gr/h/d), 3- SC (0.2 gr/h/d) and 4- MOS + SC. Sheep were fed a diet based on 40 : 60 of alfalfa hay : whole grain barley. Periods were 18 days with the last 8 d for in situ incubations of barley grain, alfalfa hay and mixture of barley grain and alfalfa. Incubation run in duplicate for each substrate and each hour. Total volatile fatty acids (VFA) concentration and individual VFA proportions and NH3-N were similar among treatments ( P 0.05). Sheep fed MOS + SC had significantly lower ruminal pH and alfalfa degradability than other treatments. Effective degradability of barley grain was also reduced when MOS + SC was supplemented. Meanwhile, total potential degradability and potentially degradation of dry matter of alfalfa decreased in SC-fed sheep. Results showed that generally supplemental MOS or SC was inefficient to improve the in situ degradability of fibrous and non-fibrous feedstuffs, However, MOS reduced ruminal pH when combined with SC. In the experiment 3, 8 multiparous Holstein cows (27 ± 6.2 days in milk) were fed diets based on alfalfa hay and barley grain in a 2 replicated 4 × 4 Latin square design. Treatments were as noted in experiment 2. Periods were 21 d in length with the last 7 days for recording and sampling. Additives had no effect on dry matter intake and milk production. Milk protein percentage was higher in MOS + SC fed cows, though milk protein yield was similar. Supplemental SC and SC + MOS increased apparent digestibility of dry matter (DM) and