There is a growing concern over the use of antimicrobial drugs in poultry feed due to the risk of potential resistance of pathogens and the accumulation of antibiotic residues in meat. The present study was designed to compare the effect of an antibiotic, an organic acid and a probiotic on performance traits, blood biochemical parameters, ileal histology and antioxidant status in broilers during finishing phase exposed to Clostridium perfringens challenge. A total of 480 day-old broiler chicks (Ross 308) was randomly allocated to six treatments with eight replicates as follows: control (basal diet); T1: infected with Clostridium perfringens; T2: infected + Avilamycin at the rate of 0.2 g/kg; T3: infected + organic acid blend; T4: infected + consisting of a probiotic, Bacillus subtilis; and T5: infected + organic acid + probiotic. Results showed that body weight and feed conversion ratio (FCR) increased significantly (P<0.05) in T4 and T1 during fourth and third week, respectively. Further, results revealed that blood globulin and total protein decreased significantly (P<0.05) in birds in T1, while albumin increased significantly (P<0.05) in T1 and T2 during the third week. During the fourth week albumin, protein and glucose concentration increased significantly (P<0.05) in T5. Villus height increased significantly in T4 with no significant change (P>0.05) in plasma thiobarbituric acid reactive substances (TBAR) and total antioxidant capacity (TAC). From the results, we concluded that probiotic and organic acid could be successfully used as antibiotic to sustain growth and biochemical profile in broilers challenged with C. perfringens.