A study was conducted to investigate the influence of selenium nanoparticles (SeNPS) and inorganic selenium supplementation in the drinking water on behavior, performance, and immunity of Arbor Acres ® and Ross ® 308 broilers exposed to E. coli O157:H7 1.6 × 10 8 challenge at the 10 th day of age.180 one-day-old female broilers were divided into six groups, each with 30 chicks. G1 and G4 were supplied with 1 mL SeNPS 100 mg.L -1 /L, G2 and G5 were supplied with 1 mL inorganic selenium 100 mg.L -1 /L, and G3 and G6 were supplied with non-supplemented water. Where, G1, G2, and G3 were Arbor Acres ® , while G4, G5, and G6 were Ross ® 308 broilers. A total of 1280 samples (160 sera, 160 intestinal swabs and 960 organ samples including liver, spleen, bursa, heart, breast muscles, and thymus) were collected in a study period of 38 days.A highly significant increase (p<0.01) of weight gain, feed conversion, performance index, total protein, albumin, alanine aminotransferase, aspartate aminotransferase, immunoglobulin G and M, total antioxidant capacity, malondialdehyde, and superoxide dismutase was recorded in G4 Ross ® 308 compared to other supplemented and control groups. G1 Arbor Acres ® and G4 Ross ® 308 broilers, also revealed a highly significant decline (p<0.01) in total bacterial and enterobacteriaceae counts of intestine and breast muscles compared to G2 Arbor Acres ® and G5 Ross ® 308 broilers and to controls. Photomicrographs revealed a higher degree of cellular and tissue protection in G4 and G5 Ross ® 308 compared to G1 and G2 Arbor Acres ® broilers. An improvement from SeNPS supplementation was detected on behavior, performance, bacterial load, immunological, antioxidant profiles, and tissue architecture in broilers breeds with special reference to Ross ® 308 compared to Arbor Acres ® broilers.