Salmonella enterica subspecies enterica serovar Gallinarum (SG) causes fowl typhoid (FT), a disease responsible for economic losses to the poultry industry worldwide. Experimental investigation of clinico-pathological lesions associated with experimental infection of Salmonella enterica subspecies enterica serovar Gallinarum in cockerels was evaluated base on clinical signs, haematological examination, serum biochemical assessment, gross and histological examination of the effect caused on the birds. Twenty cockerels were used after raring them from day old to four weeks before infection. Ten were subjected to the salmonella infection while other ten were used as control. This study revealed the severity of Salmonella enterica subspecies enterica serovar Gallinarum infection against multiple organs lesions to the birds which cause mortality as observed in the study after 5 days of infection with clinical signs of weakness, ruffled feathers, inappetence, difficulty in breathing, reluctance to move, loss of weight, increase temperature,watery and yellowish diarrhea. The haematology result indicates anemia, leucocytopenia, heterophilia and lymphocytopenia while the serum biochemical results showed that alanine transferase (ALT) and alkaline phosphatase (ALP) were statistically significant (P < 0.05), while aspartate aminotransferase (ASP), total protein (TP) and urea (U) were statistically insignificant (P > 0.05) in the infected group. The gross lesions observed include: pale carcasses, severely congested lungs, and whitish nodular lesions on the heart, haemorrhagic enteritis, and bloody intestinal content, bronze colouration of the liver, swollen kidney and enlarge spleen (splenomegaly). The histopathological lesions revealed neuronal necrosis, necrosis of the myocardium, sloughing of the intestinal villi, severe necrosis of the renal tubules, thickening of alveolar septae and bronchiolar epithelial lining, necrosis of the hepatocytes and congestion and splenic lymphocytic depletion. These findings showed the severity of Salmonella enterica subspecies enterica serovar Gallinarum on the organs of the cockerel birds (young birds) just as it does in adult birds.