Chronic medical conditions (i.e., chronic widespread pain) may contribute to accelerated/accentuated aging, such that middle-aged individuals with comorbidities may actually show increased declines in physical, cognitive, and mental health compared to normal aging adults. We examined perceived stress, life stressors, and depression in adults with and without fibromyalgia, a chronic pain condition. Ninety-four participants (52% with fibromyalgia, 78% female) aged 50 to 93 were administered the Perceived Stress Scale, Social Readjustment Rating Scale, and Beck Depression Inventory. Hierarchical regression analyses were conducted: the predictor variables were age, gender, fibromyalgia status, depression, and fibromyalgia–depression interaction. The interaction term significantly predicted perceived stress, but not life stressors. Depression significantly predicted stress for Social Readjustment Rating Scale measures after controlling for covariates. Significant associations were found between perceived stress and life stressors in all participants. In addition, those with fibromyalgia were significantly more likely to report higher levels of stress above standardized scores on both the Perceived Stress Scale and the Social Readjustment Rating Scale. Finally, depressive symptoms played a more significant role than fibromyalgia status in predicting life stressors. Conclusions: These findings emphasize the importance of assessing different types of stress and stressors in individuals with chronic widespread pain and/or depression in mid-life and beyond to better treat individuals with these conditions.