Background: Memory deficits are very common in epilepsy, but no standard of care exists to effectively manage them. Objective: We assessed effectiveness of cognitive rehabilitation (CR) on memory and neural plasticity in people with epilepsy (PWE) reporting memory impairments. Methods: Nine PWE completed 6 weekly sessions adapted from 2 generic CR programs enriched with information regarding epilepsy. Participants completed neuropsychological, mood, and quality of life (QOLIE-31) measures prior and after completion of CR; 5/9 participants also completed pre- and post-CR fMRI while performing a verbal paired associates learning task. FMRI data were analyzed using group spatial independent components analysis methods; paired t-tests compared spatial activations for pre-/post-CR. Results: Improvements were seen in immediate recall in Rey Auditory Verbal Learning Task, QOLIE-31, and read word recognition in paired associates task (all p's≤0.05). FMRI changes comparing pre-to-post CR were noted through increased activation in the left inferior frontal gyrus (IFG) and anterior cingulate and decreased activation in the left superior temporal gyrus; also noted were decreased activations in the default mode network (DMN), right cingulate, right middle temporal gyrus, right supramarginal gyrus, and increased DMN activation in the left cuneus. Conclusions: This study demonstrates feasibility of conducting CR program in PWE with fMRI as a mechanistic biomarker. Improvements in cognition and cortical plasticity await confirmation in larger samples.