The study of emotional over-involvement (EOI) has focused primarily on its relationship with patients' course of illness. The authors know little about the predictors and possible consequences of EOI for caregivers. Based on past research, they tested the hypotheses that EOI is associated with worse physical and psychological health among caregivers and examined whether caregiver burden and social support may mediate this relationship. In a sample of 37 Mexican American caregivers and their ill relatives recruited from two outpatient clinics, the authors examined the relationships between EOI, caregiver burden, caregivers' level of social support, and caregivers' health. Additionally, they examined whether caregiver burden and social support may mediate the relationship between EOI and caregivers' health. Cross-sectional analysis indicates that at baseline EOI was not associated with caregiver burden or social support, but was related to worse current health. Longitudinal analysis, however, indicates that EOI at baseline was associated with greater burden, less instrumental support, and worse health among caregivers at follow-up. Moreover, objective burden and instrumental support mediated the relationship between EOI and several health outcomes. Consequently, EOI may be a marker of poor current health status and predicts worse future health among Mexican–American caregiving relatives of individuals with schizophrenia. Moreover, changes in burden and social support associated with EOI appear to mediate the relationship between EOI and several health outcomes among caregivers. These findings suggest that it might be important for family interventions to not only address the functioning of individuals with schizophrenia but also their caregiving relatives.