Typhoid fever is systemic illness caused by Salmonella enterica serovar Typhi (S. Typhi) in humans. Increasing multidrug resistant strains of S. Typhi and limited effect of available vaccines has necessitated exploring of new immunogens for protection against it. Earlier studies have shown that a crude preparation of outer membrane proteins (OMPs) of S. Typhi evokes strong immune response and induces a protective immunity against infection caused by diverse Gram-negative bacteria. In the present study we have evaluated the protective effect of a purified recombinant 49 kDa (r49kDa) OMP of S. Typhi alone or along with alum or complete Freund's adjuvant, against a challenge by S. Typhi (0.4 Ă 50% lethal dose) by biochemical estimation of serum enzymes and oxidative stress enzymes in Swiss albino mice. There was a decrease in activity of alanine aminotransferase by 14.28%, 38.09%, 23.80%; aspartate aminotransferase by 6.25%, 25%, 16.25%; lipid peroxidation by 4.34%, 18.84%, 11.59%; and catalase by 8%, 14%, 10%, respectively, whereas increase in activity of reduced glutathione by 33.33%, 61.11%, 44.44%; glutathione peroxidase by 7%, 16%, 10%; and glutathione reductase by 8%, 20%, 12%, respectively, as compared to control animals challenged with bacteria without pre-immunization. The results indicated that immunization of mice with r49kDa OMP alone or in combination with adjuvants protected and normalized the liver. It reduces the development of oxidative stress in mice against Salmonella infection and the risk of getting typhoid. These results represent an additional supplement to our earlier reported data on protective immunity evoked by this protein.