Thirty-one mothers of infants with sickle cell anemia (n = 14) or sickle cell trait (n = 17) were interviewed to investigate the psychological stress they experienced and the coping strategies they used when first learning their child's diagnosis and when presently caring for their child. All children were diagnosed with sickle cell conditions through newborn screening. Mothers of children with sickle cell disease most often reported the expectation of pain for their child as a stressor, whereas mothers of children with sickle cell trait most often reported uncertainty of the diagnosis as a stressor. Although sickle cell trait is not a life-threatening condition, mothers of these infants reported a great deal of stress in regard to the health of their children and to their own ability to manage such stress. Mothers in both groups reported using Positive Reappraisal, Seeking Social Support, Self-Control, and Planful Problem Solving most frequently to cope with present stressors. The results also have implications for the use of newborn screening.