This study aimed to demonstrate the effect of Clostridium perfringens (Cl. perfringens) infection on broiler chickens. Also, to compare between the effect of amoxicillin and / or organic acids on Cl. perfringens infection through the evaluation of hemogram, blood chemistry, hepato-renal functions and immune response using ELISA technique. One hundred, one-day old Hubbard chicks were divided into five equal groups. Group 1: negative control, Group 2: infected broilers with Cl. perfringens type A (1.9×10 9 organism/mL), Group 3: infected chickens and treated with amoxicillin [15 mg/kg body weight (B.W.)] for 5 successive days, Group 4: chickens were administered organic acids (1 mL /L water) then were infected and Group 5: infected chickens then treated with both amoxicillin and organic acids. Cl. perfringens infection resulted in decreased appetite, ruffled feathers and brownish diarrhea with sudden death in some cases with a mortality rate up to 25%. Birds infected and treated with amoxicillin showed mild clinical signs with 15% mortalities. Majority of chickens supplemented with organic acids or with organic acids and amoxicillin followed by Cl. perfringens infection showed depression with a mild diarrhea and 10% mortality rate. Chickens infected with Cl. perfringens had macrocytic hypochromic anemia, leukocytosis, heterophilia and monocytosis. In addition, a significant decrease of total protein, albumin, phagocytic % and phagocytic index with a significant increase of total golbulins, liver enzymes activities, serum uric acid, creatinine and glucose levels were reported. Treatment of Cl. perfringens infection with amoxicillin, organic acids alone or their combination resulted in a positive effect in treatment, ameliorating the severity of infection and a significant improvement in some immunological and biochemical parameters. In conclusion, the combination of amoxicillin and organic acids showed the best results as it returned all hematological, biochemical and immunological parameters to their normal levels.