The effect of sex and temperament on response of crossbred beef calves to a commercially available Salmonella vaccine was studied. Exit velocity (m/s) and pen score (1 = calm and 5 = excitable) data collected from calves 28 d before weaning were used for assignment to 1 of 3 temperament classes (calm, n = 31; intermediate, n = 44; temperamental, n = 31). Calves, stratified by temperament class and sex, were assigned to non-vaccinated (control, n = 54) and vaccinated (n = 52) groups. Vaccinated calves received 2 mL of Salmonella Newport extract vaccine (Zoetis, Florham Park, NJ) twice: at weaning (d 0) and 28 d after weaning. Body weights were recorded on d 0, 28, and 56 and blood samples were taken at 7-d intervals to determine serum cortisol concentration by RIA and Ig ratio specific to the vaccine by ELISA (Epitopix, MN). Weight and age data were analyzed with mixed model procedures of SAS; sex, temperament class, and vaccine group were included as fixed effects. Average age at weaning did not differ between treatments (P = 0.2; 200 ± 3.9 d). Vaccination did not affect weight gain from d 0 to 28 (P = 0.33; 7.21 ± 0.9 kg) or d 0 to 56 (P = 0.4; 24.61 ± 1.1 kg). As there was no difference in performance due to vaccination only vaccinated calves were used in the remaining analysis. A specific Ig profile of each calf was assessed for maximum height for both initial (Ig1; d 0 to 21) and booster vaccination (Ig2; d 28 to 56). Neither sex (P > 0.19) nor temperament (P > 0.07) influenced peak Ig1 (0.34 ± 0.06), peak Ig1d (15 ± 1.5 d), peak Ig2 (0.70 ± 0.03), or peak Ig2d (41 ± 2.7 d). Cortisol and Ig ratio during the study were analyzed as repeated measures; the models included temperament, sex, and day as fixed effects. Temperament did not affect average cortisol (P = 0.29) or average Ig ratio (P = 0.50). Male relative to female calves had lower average cortisol (P < 0.01; 31.5 ± 2.8 vs 55.7 ± 2.8 ng/mL) and greater average Ig ratios (P = 0.04; 0.44 ± 0.03 vs 0.34 ± 0.03). Sex of calf influenced the adaptive immune response to Salmonella Newport extract vaccine.