A study was structured to evaluate the effect of selenium and vitamin E supplementation on the humoral immune response to hemorrhagic septicemia (HS) vaccination in calves. Twenty unvaccinated calves, two to four months old were randomly selected and divided into four groups, each group consisting five calves. Group A was control; Group B was vaccinated against HS, Group C was supplemented with selenium and vitamin E (VESS) and Group D was vaccinated against HS along with VESS. Groups C and D were supplemented with VESS on day 0 of experimental trial. After fifteen days, vaccine was administered to Groups B and D. Blood samples were collected at day 0, 30 and 45 from each animal and serum was separated by centrifugation. Antibody titer was determined by complement fixation test. One-way analysis of variance and Tukey’s post hoc test were used for statistical analysis of data with 0.05 as level of the significance. Results showed significantly higher antibody titer (P<0.05) in Group D as compared to Group B at day 45 of experimental trial. It was concluded that selenium and vitamin E significantly improve the antibody titer when given along with HS vaccine in calves.