A total of 200 one-day-old male broilers were assigned to five groups, and each group consisted of four replicates with 10 birds per replicate. Chicks were fed the basal diet with 0 (non-infected control), 0 (infected control), 10, 20, and 40 mg/kg soybean isoflavones (SI) for 42 days. At 21 days of age, chickens were inoculated with an infectious bursal dose (causing 50% morbidity) of the infectious bursal disease virus (IBDV) BC 6/85 strain by the eye-drop and nasal route (except for the non-infected group). Average daily gain (ADG) and average daily feed intake (ADFI) decreased (p < 0.05) in broilers infected with infectious bursal disease virus (IBDV) from 22 to 42 days. However, infected broilers fed 10 and 20 mg SI/kg had the maximum (p <0.05) ADG and ADFI from 1 to 42 days. Body weight (BW) increased (p < 0.05) in infected broilers fed the 10 and 20 mg SI /kg diet. The bursa weight at 7 days post-infection (dpi) was increased (p < 0.05) by the supplemental 10 mg SI/kg diet. Infected broilers showed the highest (p < 0.05) bursa lesions, with an average score of 4.0 ± 0.0, while the severity of bursa lesions was decreased (p < 0.05) at 3 dpi and 7 dpi by the supplemental 20 mg SI/kg diet. Supplemental SI at 20 mg/kg decreased (p < 0.05) the viral protein 5 (VP5) mRNA expression at 3 dpi and 7 dpi. The level of interferon gamma (IFNγ) was elevated (p < 0.05) in the infected group at 3 dpi and 7 dpi as compared with the control group, while its level was decreased (p < 0.05) by supplemental 10 mg/kg SI at 3 dpi. The level of nuclear factor κB in the bursal tissue showed the lowest value (p < 0.05) with supplemental 10 and 20 mg SI/kg diet at 7 dpi. Supplemental 10, 20, 40 mg/kg SI improved (p < 0.05) the serum total antioxidant activity (T-AOC) in infected broilers at 3 dpi. In addition, the serum level of malondialdehyde (MDA) decreased (p < 0.05) in the group fed 20 mg/kg SI at 7 dpi. In conclusion, supplemental 10~20 mg/kg SI may have a positive effect on broiler chickens infected with IBDV, probably because SI decrease the severity of bursa lesions and viral protein 5 mRNA expression, and have strong antioxidant activity.