Bipolar Disorder (BD) is a chronic mood disorder with a prevalence estimated around 1–2%. Bipolar patients may experience social and working residual impairment even during euthymia. Furthermore, specific cognitive deficits, particularly involving working memory (WM), may persist during eythymia as well. To evaluate the possible presence of cognitive and functional differences between euthymic bipolar subjects vs. healthy controls during euthymia by means of a WM task at fMRI associated with neuropsychological evaluations. A sample of 30 subjects aged between 20 and 45 years (15 with BD and 15 controls) underwent fMRI examination at 3 Tesla with tasks of working memory (n-back). All participants received a neuropsychological evaluation, inlcuding Stroop Color-Word Interference test, Tower of London, Trail Making Test, Wisconsin Card Sorting Test and Verbal Fluency Test. Comparison tests were performed using statistical software SPSS and SPM5. The performance of the control group was significantly higher than both at the n-back task and at the neuropsychological tests. The full-factorial analysis of fMRI data showed a hypoactivation in bipolar patients in particular hippocampus and thalamus, associated with increased involvement of areas not involved in the frontal-parietal networks classically associated with WM. The results seem to confirm the existence of a residual dysfunction during euthymia phase in BD, suggesting two distinct patterns of activation in the two groups studied, both from a neuropsychological point of view and from a neuroimaging perspective.