The present study was conducted to evaluate the therapeutic effects of ceftriaxone on colibacillosis-induced infection in broilers. Besides, the effects of both colibacillosis infection and ceftriaxone treatment on the body performance and immune parameters of broilers were evaluated. A total of 200 one-day-old broiler chicks (100 healthy, and 100 experimentally challenged with E. coli) were used in this investigation. Broilers were divided into four equal groups (n= 50 /each). Group (G1): healthy broilers were kept as a control group. G2: healthy broilers that received a therapeutic dose of ceftriaxone. G3: broilers were experimentally infected with E. coli with no treatment. G4: broilers were experimentally infected with E. coli and received a therapeutic dose of ceftriaxone. The obtained results revealed that challenged broilers with E. coli showed significant decreases in body weight, weight gain, phagocytic percentage, phagocytic index, total protein, albumin, β, γ globulin, total globulin, Superoxide dismutase (SOD), and Glutathione peroxidase (Gpx). Besides, insignificant decreases in lymphocytes, basophils, eosinophils, and monocytes coupled with increases in food conversation ratio (FCR), WBCs, heterophils, nitric oxide, and lysosome, A/G ratio, malondialdehyde (MDA) were recorded in comparison to the control broilers. Infected broilers treated with ceftriaxone showed significant improvement in body weight, weight gain, total protein, albumin, γ globulin, and total globulin. Moreover, other parameters such as WBCs, α, and β globulin, MDA, FCR, heterophils, nitric oxide, lysosome, phagocytic percentage, and phagocytic index, A/G ratio, Tumor necrosis factor α (TNF-α), Interleukin 10 (IL-10), Gpx, and SOD were significantly improved compared with the challenged birds with no treatment. Such results demonstrated the colibacillosisinduced adverse effects on broilers and the use of ceftriaxone as an effective therapeutic candidate