The present study was conducted to determine the effects of dried distillers grains with soluble (DDGS) inclusion in lamb fattening diets replacing (partially or totally) soybean meal (SBM) as a protein source and corn as an energy source on growth performance, digestibility, rumen liquor traits, some blood plasma constituents, and economic efficiency. Twenty ¾ Romanov × ¼ Rahmani male lambs at about three months of age were divided randomly into four experimental groups with average live weight (17.7 ± 0.7 kg). Each lamb's group was randomly assigned for one of four experimental diets and was fed in group feeding in mash form. The complete diets comprised 40% clover hay (CH) and 60% concentrate feed mixture (CFM) containing 0% DDGS (T1, control), 10% DDGS (T2), 15% DDGS (T3) or 20% DDGS (T4). The main results showed that the DDGS contained 29% CP, 10% EE, 10% CF, 46% NFE ,5% ash, 18% ADF, 44% NDF, 26% hemi-cellulose, 14% cellulose, 4.1% ADL and 12% NFC. All the total mixed diets had nearly equal values for chemical nutrients except that of NFE content. The inclusion of DDGS in lamb's diets at 10, 15 and 20% resulted in better digestion coefficients of all nutrients and nutritive value as TDN and DCP% in comparison with the control group. The same trend was found also in the concentrations of energy (DE, ME and NE Mcal /kg). Ruminal pH values and NH3-N were slightly changed among treatments. However, VFA's concentrations (meq/100ml) was gradually increased (P≥0.05) with elevating the DDGS level in the diets. The lambs of T1 and T2 recorded nearly similar values of average daily gain; ADG (163.1 and 161.3g), however, those of T3 and T4 had higher ADG (181.0 and 192.0g) than the control by about 11.0 and 17.7%, respectively. The intake of TDN and DCP were gradually increased with elevating DDGS level in the diet from 0 up to 20%. The DDGS inclusion in lamb diets did not show positive effects concerning feed conversion as g TDN or g DCP/g gain, meanwhile, the lambs of T3 and T4 recorded better values of DM conversion than the control (T1) by about 7.1 and 9.8%, respectively. Economic efficiency was gradually improved with elevating DDGS level in the diet where it was better for T2, T3 and T4 groups than the control (T1) by about 11.0, 34.6 and 45.6%, respectively. It may be concluded that in general, the inclusion of DDGS instead of corn and SBM at any level resulted in better performance, feed utilization and economic efficiency.