This study aimed to demonstrate the effect of Cl. perfringens infection on broiler chickens and compares 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 through ELISA technique. One hundred one-day old chicks were divided into five equal groups. Group (1): negative control, Group (2): Clostridium perfringens type A (1.9×109 organism/ml) infected broilers, Group (3): infected chickens treated with amoxicillin (15 mg/kg. wt.) for 5 successive days, Group (4): chickens administered organic acids (1 mL /L water) then infected and Group (5): chickens infected and 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 followed by Cl. perfringens infection or with organic acids and amoxicillin showed depression with a mild diarrhea and 10% mortality rate. Chickens infected with Cl. perfringens had macrocytic hypochrmic anemia, leukocytosis, heterophilia and monocytosis. In addition to, 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. Treatment of Cl. perfringens infection with amoxicillin, organic acids alone or in combination resulted in a positive effect in treatment, ameliorating the severity of infection and a significant improvement in some immunological and biochemical parameters, the best results were observed with combination.