Depression is a debilitating mood disorder, associated with impaired memory and a negativity bias, where negative events are better remembered than positive or neutral events. Impaired hippocampal pattern separation, a computation supporting memory for unique events, has been proposed as a mechanism underlying cognitive dysfunction in depression. Mnemonic discrimination tasks tax hippocampal pattern separation, offering insight into mechanisms underlying memory deficits in depression. Antidepressants are the first-line pharmacological treatment for depression and target specific neurotransmitters that can impact the hippocampus and surrounding medial temporal lobe regions. However, there is limited research examining the influence of antidepressants on memory and hippocampal function in humans. This study utilized high-resolution neuroimaging to examine hippocampal activity during emotional memory in individuals taking antidepressants. Results showed differing hippocampal activity based on antidepressant type and treatment response, suggesting that these factors can have unique impacts on emotional memory and the underlying neural mechanisms of depression.