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Birds (364) of both sexes, 11-wk-old, belonging to 2 native (Brown Nicobari and Ghagus) breeds and 1 exotic breed (Dahlem Red) were evaluated for cell-mediated immune response (CMI) by phytohemagglutinin-P (PHA-P), hemagglutination inhibition (HI) assay against Newcastle disease virus (NDV) antigen (LaSota stock virus), flow cytometric analysis of CD8+ cytotoxic T lymphocytes (CTLs), and hematology and biochemical assays. The cutaneous basophil hypersensitivity response PHA-P% increase in wattle thickness (mm) was highest in Ghagus (431.14 ± 22.56) which differed significantly with that of Brown Nicobari (269.1 ± 22.66) and Dahlem Red (218.42 ± 22.30). Sex-wise observation showed that females are having significantly higher response than males. Hemagglutination inhibition test was performed to determine the serum antibodies against Newcastle disease (ND) virus. Brown Nicobari showed highest HI antibody titer than Ghagus and Dahlem Red to similar vaccination program after booster NDV dose. Flow cytometry assay revealed significantly higher CTLs proliferation in Brown Nicobari than Ghagus and Dahlem Red. Moreover, CTLs were found to be higher in control group than the treatment group. Other hematological parameters (103/μL) significant difference was found in white blood cell count between Dahlem Red (38.41 ± 1.03) with that of Brown Nicobari (35.28 ± 1.04) and Ghagus (34.57 ± 1.04) in treatment groups. Same trend was observed in the Lymphocyte treatment group. However, in Granulocyte treatment group, Brown Nicobari (11.04 ± 0.35) was found to be significantly different from Dahlem Red (8.68 ± 0.34) and Ghagus (9.27 ± 0.35). Correlations between body weight at 11 wk of age and CMI, HI, cytotoxic T cell were −0.093, 0.047, and −0.036, respectively. Egg weight was found to be positively correlated with that of chick weight. Serum biochemical values showed that Dahlem Red was having significantly higher creatinine levels compared to Ghagus. Triglycerides level was also significantly higher in Ghagus compared to Dahlem Red. No significant breed effect was observed for alkaline phosphate, aspartate transaminase, and alanine transaminase. Cholesterol and total serum protein levels were significantly higher in Dahlem Red compared to Brown Nicobari.