Objective: Previous studies have compared depressive episodes between bipolar disorder (BD) and major depressive disorder (MDD) using quantitative electroencephalogram (QEEG); however, there are no distinct discriminating feature between them. Here, we used QEEG to directly compare the alpha asymmetry and absolute power of each band between patients with BD and MDD.Methods: Fifty in-patients with major depressive episodes between 2019 and 2021 were retrospectively enrolled. Self-reported questionnaires including the Beck Depression Inventory (BDI), Korean version of the Childhood Trauma Questionnaire, and Adult Attention-Deficit/Hyperactivity Disorder Self Report Scale (ASRS) were used to evaluate the symptoms. The absolute power of QEEG delta, theta, alpha, beta, high beta waves, and the Z-scores of frontal alpha asymmetry were collected. A t-test and Pearson’s correlation test were conducted using these data and based on these results, an analysis of covariance was conducted.Results: There were no significant differences between MDD and BD in QEEG power or alpha asymmetry. Patients with severe depression (BDI ≥29) had higher alpha power at FP1 (p=0.037), FP2 (p=0.028), F3 (p=0.047), F4 (p=0.016), and higher right frontal alpha asymmetry at F3–F4 (p=0.039). Adult patients with features consistent with ADHD (ASRS ≥4) had higher right frontal alpha asymmetry at F3–F4 (p=0.046). Patients with insomnia had higher left frontal alpha asymmetry at F3–F4 (p=0.003).Conclusion: QEEG limited the differential diagnosis of MDD and BD. However, frontal alpha asymmetry did exist in depression and affected cognitive impairment, insomnia, and depression severity in particular. Future studies with improved methodologies are needed for a better comparison.