OBJECTIVES: Pain and its disruptive impact on daily life are common reasons that patients seek primary medical care. Pain contributes strongly to psychopathology, and pain and depressive symptoms are often comorbid in primary care patients. Not all those who experience pain develop depression, suggesting that the presence of individual-level characteristics, such as positive and negative affect, that may ameliorate or exacerbate this association. METHODS: We assessed the potential moderating role of positive and negative affect on the pain-depression linkage. In a sample of 101 rural, primary care patients, we administered the Brief Pain Inventory, NEO Personality Inventory-Revised positive and negative affect subclusters, and the Center for Epidemiology Scale for Depression. RESULTS: In moderation models, covarying age, sex, and ethnicity, we found that positive affect, but not negative affect, was a significant moderator of the relation between pain intensity and severity and depressive symptoms. DISCUSSION: The association between pain and depressive symptoms is attenuated when greater levels of positive affects are present. Therapeutic bolstering of positive affect in primary care patients experiencing pain may reduce the risk for depressive symptoms.