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Objective Evaluate depressive symptoms in caregivers of children with type 1 diabetes (T1D) or cystic fibrosis (CF) and identify associated risk factors. Methods A total of 195 caregivers completed demographic, stress, and depressive symptoms questionnaires. Children’s health status was obtained from medical records. Results Approximately 33% of caregivers reported elevated symptoms of depression (i.e., exceeded clinical cutoff of 16 on the Center for Epidemiological Studies-Depression Scale). For caregivers of children with T1D, elevations were associated with less caregiver education, more family stress, older child age, and worse glycemic control. For caregivers of children with CF, more family stress and lack of employment outside of the home were associated with elevated depressive symptoms. Conclusions Many caregivers of children with T1D or CF experience depressive symptoms, although risk factors may differ in these two populations. Screening of caregiver depressive symptoms as part of routine clinic visits may provide opportunities for needed intervention.