Background Neural substrates of bipolar disorder (BD) have frequently been characterized by dysregulation of fronto-limbic networks that may persist during euthymic periods. Only a few studies have investigated euthymic bipolar patients (BP) functional connectivity at rest. The current study aims to assess resting-state functional connectivity in euthymic BP in order to identify trait abnormalities responsible for enduring mood dysregulation in these patients. Methods Medial prefrontal cortex (mPFC) functional connectivity was investigated in 20 euthymic BP and 20 healthy subjects (HS). The functional connectivity maps were compared across groups using a between-group random effect analysis. Additional region of interest (ROI) analysis focused on mPFC–amygdala functional connectivity as well as correlations between the clinical features in euthymic BP was also conducted. Results A significant difference between euthymic BP and HS was observed in terms of connectivity between the mPFC and the right dorsolateral prefrontal cortex (dlPFC). A significant negative correlation between the activity of these regions was found in HS but not in euthymic BP. In addition, euthymic BP showed greater connectivity between mPFC and right amygdala compared to HS, which was also correlated with the duration of the disease. Limitations The BP group was heterogeneous with respect to the bipolarity subtype and the medication. The robustness of results could be improved with an increased sample size. Conclusions Compared to HS, the euthymic BP showed abnormal decoupling (decreased functional connectivity) activity between mPFC–dlPFC and hyperconnectivity (increased functional connectivity) and between mPFC and amygdala. These abnormalities could underlie the pathophysiology of BD, and may deteriorate further in accordance with disease duration.