Animal studies have shown that an acute stressor in close temporal proximity to immune challenge can enhance the response to delayed-type hypersensitivity and antibody response to vaccination. The current study examined the effects of acute exercise or mental stress prior to influenza vaccination on the subsequent antibody response to each of the three viral strains. Sixty young healthy adults (31 men, 29 women) were randomly allocated to one of three task conditions: dynamic exercise, mental stress, or control. After an initial baseline, participants completed their allocated 45 min task and then received the influenza vaccine. Plasma cortisol and interleukin-6 were determined at the end of baseline, after the task, and after 60 min recovery. Antibody titres were measured pre-vaccination and at 4 weeks and 20 weeks post-vaccination follow-ups. For the A/Panama strain, women in both the exercise and mental stress conditions showed higher antibody titres at both 4 and 20 weeks than those in the control condition, while men responded similarly in all conditions. Interleukin-6 at +60 min recovery was found to be a significant predictor of subsequent A/Panama antibody response in women. In line with animal research, the current study provides preliminary evidence that acute stress can enhance the antibody response to vaccination in humans.