Newcastle disease (ND) remains one of the most harmful poultry diseases that threaten the poultry industry producers all over the world, thus the present work was planned to investigate the hematological, biochemical, and pathological changes in vaccinated and non-vaccinated broiler chickens naturally infected with ND. The study was conducted on 45 broiler chickens, 35-days-old, from a private farm in Damietta governorate and used in this work, 15 chickens were clinically healthy (Group I), 30 chickens with ND symptoms divided into 15 non-vaccinated (Group II) and the other 15 chickens (Group III) were vaccinated with La Sota strain of NDV with a titre of 106.5 EID50. The disease was diagnosed by hem agglutination test as ND. Blood and tissue samples were collected for clinical-pathological and histopathological examination. The infected broiler chickens showed cyanosis, nasal discharge, edema of eyelid and white pasty diarrhea with nervous manifestations. Furthermore, microcytic hypochromic anemia with leukocytosis was observed. Biochemical studies revealed a significant decrease in serum total proteins, albumin and A/G ratio, with significant increases in serum activities of aspartate aminotransferase, creatinine, and uric acid and glucose concentration in addition to several histological alterations were significantly seen in brain, intestine, liver and kidney of the infected birds. All these disturbances were less severe in the vaccinated group than the non-vaccinated one. In conclusion, La Sota vaccine can increase the bird resistant against Newcastle disease virus induced blood disorders and hepatic-renal insufficiency in broiler chickens. Keywords: Newcastle disease virus, Broilers, La Sota, Hematobiochemical, Histopathology