In this study, the effect of replacement of fish meal with soybean meal and baker's yeast on activity of digestive enzymes, body composition and biochemical blood factor of juveniles (Mesopotamichthys sharpeyi) were studied. Five treatments consisted of a control treatment (no Soybean meal and yeast) and treatments containing 25%, 50%, 75% and 100% replacement of fish meal with soybean meal and baker's yeast with ratio of 1:1 in triplicates were examined. Each replicate were stocked with 40 fish with initial average weight of 4.40 ± 0.29 g in 300 liter tank with a volume of 250 liter of water. Experimental fish were fed to satiation triple daily for 56 days. At the end of the period, the activity of digestive enzymes were not significantly different compared with control group (P>0.05).   The carcass biochemical composition of fish in different treatments were not significantly different compared with the control group (P>0.05). Triglycerides value of plasma were significantly decreased and total cholesterol were significantly increased with replacement of fishmeal in diet compared with the control group (P <0.05). So, soybean meal and baker's yeast with same ratio can be used up to 100% instead of fish meal without negative effect in the diet of juveniles Mesopotamichthys sharpeyi.