The complex management of ventilator-assisted children cared for in the home can place emotional and mental strain on parents, in particular, mothers. The purpose of this study was to explore the relationships among functional status of the child, impact of ventilator-assistance on the family, coping, social support, and depression in mothers caring for ventilator-assisted children at home. Thirty-eight mothers participated in the study. Almost half of the mothers experienced depressive mood symptoms. Impact on family was positively related to depression and social support was inversely related to depression. In addition, social support was a significant predictor of depression. The findings show that the high demands related to the care of ventilator-assisted children can be a significant risk factor for poor mental health outcomes of those mothers providing care at home. Interventions by mental health and pediatric nurses should focus on enhancing mothers' coping skills and assisting mothers in accessing a positive social network to help mediate the stress related to caring for their child.