BACKGROUND: Patients with bipolar disorder (BD) and major depressive disorder (MDD) often exhibit cognitive impairments, with choroid plexus (ChP) volume linked to these deficits and cortical structures. However, the relationship between ChP volume, cognition, and brain morphology in mood disorders remains understudied. This study aimed to investigate these mechanisms. METHOD: The study included 216 BD patients, 316 MDD patients, and 268 healthy controls who completed questionnaires, cognitive tests (e.g., the Symbol Digit Modalities Test (SDMT), the Verbal Fluency Test (VFT), the Chinese Revised Wechsler Memory Scale), and MRI scans. ChP volume, subcortical volume, and cortical thickness were measured, with group differences analyzed and correlations examined and compared. RESULTS: BD and MDD patients had significantly larger ChP volume than healthy controls, with no difference between patient groups. In both groups, ChP volume negatively correlated with subcortical volume (r = -0.021 ~ -0.285, q <
0.05) and cortical thickness (r = -0.149 ~ -0.317, q <
0.05). Furthermore, ChP volume negatively correlated with logical memory (r = -0.154 ~ -0.161, q <
0.05) and positively with visual reproduction (r = -0.159, q = 0.043) in BD, while negatively correlated with the SDMT (r = -0.122 ~ -0.152, p <
0.05) and VFT (r = -0.118, p = 0.015) in MDD. Associations between ChP volume and right precentral gyrus thickness and memory quotient differed between the two groups. CONCLUSION: Enlarged ChP volume in mood disorders was associated with brain atrophy and cognitive deficits, suggesting it could serve as a marker for structural and cognitive changes.