The goal of this study was to find out how supplementing rabbits with cinnamon Nanoparticles (CNP) affected their immunity, growth performance, serum biochemistry, blood haematology, and the histology of their liver, lung, and kidney in addition to their protective impact against a fake infection with Escherichia coli O25. After being acclimated for two weeks and separated into six equal groups, sixty weaned white New Zealand rabbits (35 days old) that appeared healthy were acquired from a private farm in Kafr EL-Sheikh Governorate. According to our findings, the rabbits that got CNP exhibited better growth performance, P.M. lesions, bacterial re-isolation outcomes, and clinical symptoms. The hepatic and renoprotective effects of CNP may be supported by the mean values of serum ALT and AST levels decreasing and mean values of total protein, albumin, globulin, total white blood cell count, lymphocyte count, and antioxidant enzymes (SOD and CAT) increasing. The histological analysis showed that the positive control group had apparent pathological changes, such as interstitial nephritis, hepatic coagulative necrosis, and interstitial pneumonia with mononuclear cell infiltrations. The CNP and streptomycin-treated group, on the other hand, showed milder to moderately changed tissue conditions. It is possible to conclude that CNP can be used as an alternative to antibiotics because the combined treated group showed high efficacy (growth performance, antibacterial, and favourable effects on liver, kidney, and antioxidant enzyme functions in addition to reducing the histological alteration changes in liver, kidney, and lung tissues).