Background: Series of more than 35 proteins facilitated a major role in fighting the foreign invaders in human body and other warm blooded animals, those named complement system. Methods: Total of 147 human serum were collected from asymptomatic volunteers by venipuncture, their sero groups were determined by reverse blood grouping method. Strain of Salmonella typhi (S. Typhi) were collected from Wudil general hospital and identified molecularly at center of biotechnological research of Bayero University, Kano. Serum bactericidal assay was done at microbiology laboratory of Wudil general hospital. Data obtained was subjected to two way ANOVA and considered significant at p<0.05. Results: Complement dependent pathways shows a more than 50% kills, in which both A, AB, B and O kill percent were 74.98%, 67.87%, 78.53% and 78.60% respectively, however, no statistical significant difference. While the non-complement dependent pathways revealed kills percentage of 59.27%, 57.86%, 59.21% and 58.60% for A, AB, B and O sero groups, also no significant statistical difference. Moreover, in comparing the complement and non-complement dependent pathways, data analysis shows a significant difference with p values of 0.001, 0.003, 0.006 and 0.0008 for A, AB, B and O sero groups respectively. Conclusion: We concluded that, ABO sero-groups and complement system plays an important role as infection determinants, where AB sero-group have more chances to S. Typhi infection than other sero-groupings. This study suggests that the effect of many host genetic parameters on treatment of microorganisms needs to be further studied.