In the last few decades, the incidence of mood disorders skyrocketed worldwide and has brought an increasing human and economic burden. Depending on the main symptoms and their evolution across time, they can be classified in several clinical subgroups. A few psychobiological indices have been extensively investigated as promising markers of mood disorders. Among these, frontal asymmetry measured at rest with quantitative EEG has represented the main available marker in recent years. Only a few studies so far attempted to distinguish the features and differences among diagnostic types of mood disorders by using this index. The present study measured frontal EEG asymmetry during a 5-min resting state in three samples of patients with bipolar disorder in a Euthymic phase (EBD, n = 17), major depressive disorder (MDD, n = 25) and persistent depressive disorder (PDD, n = 21), once termed dysthymia. We aimed to test the hypothesis that MDD and PDD lack the typical leftward asymmetry exhibited by normal as well as EBD patients, and that PDD shows greater clinical and neurophysiological impairments than MDD. Clinical scales revealed no symptoms in EBD, and significant larger anxiety and depression scores in PDD than in MDD patients. Relative beta (i.e., beta/alpha ratio) EEG asymmetry was measured from lateral frontal sites and results revealed the typical greater left than right frontal beta activity in EBD, as well as a lack of asymmetry in both MDD and PDD. The last two groups also had lower bilateral frontal beta activity in comparison with the EBD group. Results concerning group differences were interpreted by taking into account both the clinical and the neurophysiological domains.