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Objective To examine the relationship of parent and child ratings of illness uncertainty to depressive symptomotology in children with a chronic illness using a mediational model framework. Method Mother–child dyads (N = 103 pairs) each completed measures of perceived illness uncertainty, while youth also completed a measure of depressive symptomotology. Results Maternal uncertainty was directly related to child depressive symptoms; however, this relationship was mediated by child uncertainty. Conclusion It would appear that a key mechanism by which parent-related uncertainty influences child depressive symptoms is through child uncertainty, underscoring the importance of examining cognitive appraisal variables and means of transmission in parent–child interactions.