This meta-analysis examined the effect of exercise on stress reactivity in both human and animal studies. For human studies, 47 randomized controlled trials were identified and 30 were included in the analysis, totaling over 1,200 participants. The overall weighted effect size was -0.31, indicating that exercise led to a moderate reduction in stress reactivity. For animal studies, 34 studies were identified and 27 were included, totaling over 400 animals. The overall weighted effect size was -0.33, also showing that chronic free-wheel running led to a moderate reduction in stress reactivity as measured by neuroendocrine markers. The findings provide support for using exercise programs to reduce stress responses and for studying potential mechanisms in animal models.