Maternal illness is a stressor that can disrupt family processes and contribute to negative child outcomes, and researchers have considered family variables that mediate or moderate the maternal illness-child outcome relationship. Through reliance on a diverse sample (ethnically and racially, as well as geographically), the current study expands prior literature with a focus on parent-child conflict. Specifically, associations between aspects of HIV positive mothers' illness and mother-child conflict were explored. One goal of the study was to determine if there were direct or indirect associations with aspects of mothers' HIV and mother-child conflict. HIV-positive mothers (N = 136) provided CD4 count and completed measures assessing their perceived level of physical functioning, depressive symptoms, HIV health-related anxiety, and mother-child conflict with their healthy school-age children. Path analysis considered the pattern of relationships across variables. Results showed maternal vitality and depressive symptoms were directly associated with mother-child conflict. CD4 cell count and health-related anxiety operated indirectly through maternal depressive symptoms. Mediation analyses further assessed the influence of maternal CD4 cell count on mother-child conflict behavior; results indicated an indirect effect was mediated by vitality. HIV health-related anxiety and vitality separately showed indirect effects on mother-child conflict, mediated by maternal depressive symptoms. These findings are the first to focus on mother-child conflict among children affected by maternal HIV and highlight the need for screening and intervention to address depressive symptoms among HIV-positive mothers.