The present work was carried out to study the effect of using dried distillers grains with soluble (DDGS) as a source of protein in ration formulation of buffalo calves. DDGS was included in concentrate feed mixture (CFM) at 0, 11, 16, 21 and 27% to cover 0, 20, 30, 40 and 50% of total protein, respectively. Fifty male buffalo calves averaging 320.16 kg live body weight were randomly distributed into five similar groups (10 in each) and assigned to receive five concentrate feed mixtures containing five levels of DDGS. Animals were fed CFM along with berseem hay and wheat straw at the ratios of 70: 20: 10, respectively. The feeding trail lasted 184 days, during which, five digestibility trials were carried out to determine the digestibility and feeding values of the experimental rations. In addition, samples of rumen liquor and blood serum were taken to determine some ruminal and blood parameters. Also, feed and economical efficiencies were studied. The results showed that: 1-Digestibility coefficients were significantly (P<0.05) higher in DM, OM, CP and CF with animals fed rations containing DDGS. Nutritive values expressed as TDN (%), DCP (%) and DE (Mcal/Kg DM) were significantly higher (P<0.05) for ration E (containing 27% DDGS) than the other rations. 2-Animals fed ration E (containing 27% DDGS) showed the highest TDN (77.03%) DCP (12.49%) and DE (3.40 Mcal/Kg DM) versus 65.67%, 11.00% and 2.89 Mcal/Kg DM for animals fed control ration. However, all experimental rations (containing DDGS) appeared to higher nutritive values than that of control ration. 3-The highest daily gain (1.170 Kg) was recorded with animals given ration E, which had 31.46% extra improvement and increase in weight gain. Also, animals fed experimental rations (B, C, D and E rations) tended to have better feed efficiency, showing the best feed utilization efficiency expressed as DM, TDN or DCP per Kg gain being 11.147, 8.586 and 1.392 Kg/Kg gain, respectively, for animals fed ration E. 4-Animals fed ration E (containing 27% DDGS) appeared to have the lowest feed cost/Kg weight gain (17.837 LE).The highest economical efficiency (1.233) versus the highest feed cost and lowest economical efficiency was observed with animals fed control ration (ration A). 5-All ruminal and blood serum parameters were within the normal values, showing that added DDGS in ration formulation of fattening buffalo calves had no adverse effects on serum parameters and led to get better performance of animals. Generally, it may be concluded that, the inclusion DDGS at 27% to cover 50% of total protein of concentrate feed mixture in fattening buffalo calves rations tended to produce better nutrient digestibility and feeding values. Moreover, animals fed rations containing DDGS had higher weight gains and lower feed cost with the best economical efficiency without any adverse effects on ruminal or blood serum parameters.