OBJECTIVE This study examined predictors of strategies used to cope with pain in children with sickle cell disease and their mothers. METHODS Disease severity, socioeconomic status, child adjustment and adaptive behavior, maternal psychopathology, and family functioning were examined in 55 mother-child dyads to determine the predictive potential of these factors on engagement and disengagement coping. RESULTS While controlling for socioeconomic status and psychopathology in the mothers, 15% of the variance in engagement coping was predicted by family adaptability. Disengagement coping was predicted by internalizing symptoms exhibited by the child, including a negative and pessimistic attributional style, which accounted for nearly one fifth of the variance. Finally, mothers who reported more active strategies for coping with their child's pain were more likely to endorse greater use of techniques to prevent and effectively manage pain in their children. CONCLUSIONS Neither coping strategy was predicted by severity of disease presentation in the children, suggesting the importance of psychosocial factors in adapting to childhood chronic illness and that severity of disease may not necessarily be a marker for families at risk for adjustment difficulties. Findings were interpreted to support a systemic family model in promoting active and adaptive engagement coping in caretakers of children with sickle cell syndrome.