Both cumulative adversity, an individual's lifetime exposure to stressors, and insufficient exercise are associated with poor health outcomes. The purpose of this study was to ascertain whether exercise buffers the association of cumulative adverse life events (CALE) with health in a community-wide sample of healthy adults (ages 18-50 years; women: n = 219, 29.5 ± 9.2 years; men: n = 176, 29.4 ± 8.7 years, mean ± standard deviation). Participants underwent the Cumulative Adversity Interview, which divides life events into three subsets: major life events (MLE), recent life events (RLE) and traumatic experiences (TLE). These individuals also completed the Cornell Medical Index and a short assessment for moderate or greater intensity exercise behavior, modified from the Nurses' Health Study. Results indicated that higher CALE was associated with greater total health problems (r = 0.431, p < 0.001). Interactions between stress and exercise were not apparent for RLE and TLE. However, at low levels of MLE, greater exercise was related to fewer total, physical, cardiovascular and psychological health problems (p value <0.05). Conversely, at high levels of MLE, the benefits of exercise appear to be absent. Three-way interactions were observed between sex, exercise and stress. Increased levels of exercise were related to better physical health in men, at all levels of CALE. Only women who reported both low levels of CALE and high levels of exercise had more favorable physical health outcomes. A similar pattern of results emerged for RLE. Together, these data suggest that increased exercise is related to better health, but these effects may vary by cumulative stress exposure and sex.