Background: Vaccination against schistosomiasis might be an excellent approach for its control and elimination. Despite the recent advances in identification of several potential vaccine candidates, no vaccine was validated for clinical trials.Objective: This research aims to evaluate the preventive effects of soluble egg antigen (SEA) in combination with schistosomula lung antigen preparation (SLAP) on a murine model of schistosomiasis mansoni. Material and Methods: In this study, 35 Swiss albino male mice (aged 6 to 8 weeks) were divided into five groups. Each group contained seven mice, with G1 serving as the normal control, G2 the infected control, G3 the infected and immunized by SEA, G4 the infected and immunized by SLAP, and G5 the infected and immunized by combination antigens (SLAP and SEA). All mice were infected two weeks after receiving their final dose of immunization. Seven weeks following infection, mice were decapitated in order to determine the impact of the injected antigens using determination of liver enzymes, IL10, TNF-α and schistosomal IgG, with immunohistochemical assessment. Results: Reduced liver enzyme levels were detected in various vaccinated groups, with the combined group (SLAP and SEA) experiencing the greatest reduction. The combination of SLAP and SEA resulted in the highest significant increase in IL-10 and IgG antibody and the highest significant reduction in TNF-α level among all groups. Conclusion:The combination of SLAP and SEA increased the protective immunity. This combination represents an exciting direction in vaccine research.