A 12-week feeding trial was conducted to evaluate the effect of dietary probiotic, Saccharomyces cerevisiae and Lactobacillus acidophilus at a concentration of (10⁸cfu/ml).Three isonitrogenous (300 g CP kg^-1 dry matter, DM) and isocaloric (3500Kcal metabolizable energy kg^-1 DM) diets were formulated and probiotics was supplemented in the experimental diets. Fingerlings averaging 2.80±0.05g were randomly distributed into 18 glass aquaria (160 liter) and each aquarium holding 15 fish and randomly assigned to one of six replicates of the diets and offered feed at a daily rate of 5% of the total fish biomass. After 12 weeks, fish fed the diets supplemented with the two probiotics showed significantly better final weight, body length, specific growth rate, weight gain, feed intake, feed conversion ratio and protein efficiency ratio than those fed the control diet. The highest red blood cells count (RBCs), Hemoglobin (Hb), hematocrite (Hct), and the lowest mortality rate were recorded for fish fed the diet supplemented with S. cerevisiae supplemented compared to the other two groups. Fish fed the diet supplemented with S. Cerevisiae followed by L. acidophilus recorded the lowest (P<0.001) serum transaminase enzymes (alanine transaminase, ALT and aspartate transaminase, AST). Fish fed S. cerevisiae and L. acidophilus supplemented diets showed the lowest significant (P<0.001) count of microbial content in surface and muscles of Nile tilapia.