Prior research has utilized brain imaging techniques, such as fMRI, to investigate neural processes underlying learning and memory. Past studies have also explored these processes in different mental conditions to examine how mental illness relates to brain functioning. However, few studies have investigated these patterns in individuals with multiple mental illnesses. In this study, we recruited individuals with comorbid PTSD and depressive symptoms to participate in a series of tasks requiring them to learn and remember specific cues predictive of threat in specific environments. The purpose of this study was to examine how the severity of depressive symptoms is associated with activation in brain areas involved in memory. Generally, we observed that more severe depressive symptoms were associated with differences in activation in parts of the brain involved in memory, findings that lend themselves to further investigation of how this activation is related to learning and memory performance.