Depression in adults is associated with deficits in a number of cognitive domains, however it remains less clear how early in development theses deficits can be detected in early onset depression. There are several different hypotheses about the links between cognitive function and depression. For example, it has been argued that executive function deficits contribute to emotion regulation difficulties, which in turn increase risk for depression. Further, it has been suggested that some cognitive deficits, such as episodic memory, may reflect hippocampal abnormalities linked to both depression and episodic memory. We examined these questions in adolescents participating in a longitudinal study of preschool onset depression. We measured cognitive function at adolescence using the National Institutes of Health toolbox (vocabulary, processing speed, executive function, working memory and episodic memory), and examined relationships of cognitive deficits to depression, emotion regulation, life stress and adversity, as well as hippocampal volume trajectories over three imaging assessments starting at school age. Depression related deficits in episodic memory were found. Youths with either current and past depression showed episodic memory deficits even after controlling for other psychopathology and family income. Depression severity, emotion dysregulation, and life stress/adversity all predicted episodic memory impairment, as did smaller intercepts and slopes of hippocampal growth over time. Modest relationships of depression to hippocampal volume and strong relationships between emotion regulation and both episodic memory and hippocampal volume were found. These data are consistent with prior work in adults linking depression, episodic memory, emotion regulation, life stress/adversity, and hippocampal volume in adults and suggest similar relations are evident as early as adolescence when memory systems are under development. (PsycINFO Database Record (c) 2019 APA, all rights reserved).