Chronic illness is highly prevalent among adults with children. It is therefore important to understand how parental illness may or may not have an impact on affected families. Findings thus far have suggested that differences between children with and without a sick parent are minimal, but there are individual and familial moderators of outcome. It is unclear whether these results are generalizable to single-parent families. The purpose of the present study was to examine whether maternal chronic illness affects multiple aspects of child functioning in a large, ethnically diverse sample of single-parent families compared to those not affected by illness. Potential moderators of differences, including maternal distress, parenting variables (aggravation and warmth), functional impairment related to illness, and demographic characteristics were also tested. Using data from the Child Development Study (CDS), 812 mother-child pairs were studied. Mothers completed measures of child internalizing, externalizing, and positive behaviors, while children completed a measure of depression. The results indicated that overall there were no differences between children with or without a sick mother on the measures of well-being. Higher symptom levels among both cohorts were associated with maternal distress and aggravation in parenting only. However, children with a sick mother were more likely to have a consultation due to emotional difficulties. Several areas for future work on how illness affects single-parent families were identified such as prospectively studying illnesses with a variable course and determining which protective factors promote resiliency for children in this difficult situation.