A total number of 44 growing Ossimi lambs (averaged 4 months of age and 21.59 ± 0.77 kg) were used to assess the effect of soybean meal substitution for inactive dry yeast (IDY) at levels 0, 15, 30 and 45 % on nutrients digestibility, productive performance and some serum biochemical indicators of growing lambs. The results showed that digestibility coefficients of DM, OM, CP, CF, NDF, NFE and nutritive values (DCP and TDN) were increased (P<0.05) for lambs fed IDY at levels 15 and 30 % compared to those fed 0 and 45%. The improvement in nutrients digestibility and nutritive values was higher (P<0.05) for lambs fed IDY at the level 30 % than those fed 15 %. However, the averages of nutrients digestibility and nutritive values for lambs fed IDY at levels 0 and 45 % were comparable. In addition, the averages of final body weight (FBW) were increased (P<0.05) for lambs fed IDY at the level of 30 % than those fed 0, 15 and 45 %. Also, the averages of daily gain (ADG) were increased (P<0.05) for lambs fed IDY at levels of 15 and 30 % in comparison to those fed 0 and 45%. Data showed no significant differences in averages of feed intakes of soybean straw (SSI), DM and TDM among the experimental treatments. However, the intakes of DCP and TDN were greater (P<0.05) for lambs fed IDY at the level of 30 % than those fed 0, 15 and 45 %. The averages of feed conversion (FC) of DM (FC-DM) were improved (P<0.05) for lambs fed IDY at the level 30 % compared with those fed 0 and 45% of IDY. The averages of FC-DCPI and FC-TDNI were better (P<0.05) at 15, 30 and 45 % of IDY than 0 level. The averages of serum total protein (TP) concentrations were higher (P<0.05) for lambs fed IDY at the level of 30 % than those fed the levels of 15 and 45 %. Also, serum albumin levels increased (P<0.05) for lambs fed IDY at 30 % compared with those fed levels 0, 15 and 45 %. Serum globulin concentrations were comparable among the treatments of IDY at 0, 15 and 30 %, being the lowest concentration with feeding IDY at the level of 45 %. There were significant (P<0.05) increase in serum glucose concentrations for lambs fed IDY at the level of 30 % than those fed the levels 15 and 45 %, while they were comparable with those fed IDY at 0 level. The results showed no significant differences in serum concentrations of cholesterol, triglycerides and aspartate transaminase (AST) enzyme activity among the experimental treatments. This study indicated that soybean meal substitution for inactive dry yeast (especially at 30 % level) was effective to improve nutrients digestibility and productive performance accompanying with favourable signs in serum biochemical indicators of Ossimi lambs.