One of the main Hazardous reasons the chicken sector suffers significant financial losses is Escherichia coli (E. coli). The benefits of lysozyme addition in the diet for preventing avian colibacillosis are not well understood. The purpose of the current study was to compare the effects of lysozyme dietary supplementation with antibiotic treatment in broiler chicks infected with E. coli.  Eight groups of 600 one-day-old unsexed Ross chicks were created: The first group (control) was not infected and was given a balanced diet free of additives, the second and third groups were also not infected and were treated with 50 mg and 100 mg of lysozyme, respectively, the fourth group was non-infected and treated with 10 mg avilamycin / kg diet, the fifth group was infected and non-treated, the sixth and seventh group was infected and were treated with 50 mg and 100 mg of lysozyme, respectively, and the eighth group was infected and  treated with 10 mg avilamycin / kg diet. The infection by E. coli was given orally to the chicks at days 5 and 16 days of age.  The experimental period was 35 days for all examined groups. The E. coli-infected group showed decreased phagocytic activity, dressing percentage, relative weight of thymus and bursa, and serum total antioxidant capacity. The liver enzymes, renal function tests, MDA, relative weights of the liver, heart, and spleen, as well as changes in gut morphology and intestinal microbial counts, were all significantly elevated in the same group. The lysozyme-pretreated infected chick showed improvements in body performance metrics in addition to a noteworthy reduction in the tests for renal and hepatic enzymes. Significant improvements were observed in gut morphology, intestinal microbial counts, antioxidant enzymes, and serum immunological parameters in the treated groups. It is possible to draw the conclusion that adding lysozyme (at 50 and 100 mg/kg) to the diet of broiler chickens improves their immune system, performance, and reduces the pathological lesions caused by E. coli infections.