Anxiety and depression are common in patients with Cerebral venous outflow disturbance (CVOD). Here, we aimed to explore possible mechanisms underlying this phenomenon.We enrolled patients diagnosed with imaging-confirmed CVOD, including internal jugular venous stenosis (IJVS) and cerebral venous sinus stenosis (CVSS) between 2017 and 2020. All of them had MRI/PWI scans. The Hamilton Anxiety Scale (HAMA) and 24-item Hamilton Depression Scale (HAMD) were used to evaluate the degree of anxiety and depression at the baseline and three months post-stenting. In addition, the relationships between the HAMA and HAMD scores, white matter lesions, and cerebral perfusion were analyzed using multiple logistic regressions.A total of 61 CVOD patients (mean age 47.95 ± 15.26 years, 59.0% females) were enrolled in this study. Over 70% of them reported symptoms of anxiety and/or depression. Severe CVOD-related anxiety correlated with older age (p = 0.046) and comorbid hyperlipidemia (p = 0.005). Additionally, head noise, sleep disturbances, and white matter lesions (WMLs) were common risk factors for anxiety and depression (p < 0.05). WMLs were considered an independent risk factor for anxiety based on multiple regression analysis (p = 0.029). Self-contrast displayed that CVOD-related anxiety (p = 0.027) and depression (p = 0.017) scores could be corrected by stenting, as the hypoperfusion scores in the limbic lobes of patients with anxiety and depression were significantly higher than those in patients without.CVOD-induced hypoperfusion-mediated changes in the white matter microstructure may represent an underlying mechanism of anxiety and depression in patients with chronic CVOD.