The aim of this study was to investigate some biochemical and tissue changes associated with Salmonella gallinarum infection in laying hens (LHs), and the complicities of oxidative stress (OS). Fifty LHs were assigned to two groups of 25 LHs infected with S. gallinarum (109 cfu*mL-1 of S. gallinarum) and 25 uninfected controls. Biochemical assays and histopathology were carried out following standard procedures. There was a significant loss of body weight, drop in egg production, as well as 28% mortality in the infected group. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and superoxide dismutase (SOD) activities, as well as serum total protein, globulin, total cholesterol, total bilirubin, uric acid, creatinine and malondialdehyde (MDA) levels were significantly higher, whereas serum albumin levels were significantly lower in infected LHs. There were inflammatory, degenerative and necrotic changes observed in the affected organs. Considering the significant elevation in MDA levels coupled with elevated SOD activity in the infected LHs, OS may play a significant role in the pathology of fowl typhoid and may suggest a possible treatment of infected layers with antioxidants.