This study examined the extent to which daily mood and stress were associated with pain, health care use, and work activity in 41 adults (mean age=36 years) with sickle-cell disease. Multilevel model analyses of daily diaries (M=91 days) indicated that increases in stress and negative mood were associated with increases in same-day pain, health care use, and work absences. Lagged models suggested bidirectional relationships, with evidence that pain may be the more powerful initiating variable in pain-mood and pain-stress cycles. Of importance, positive mood was associated with lower same-day and subsequent day pain, as well as fewer health care contacts, suggesting that positive mood may serve to offset negative consequences of pain and other illness symptoms.