〔Abstract〕 Objective To explore the risk factors and alterations in functional connectivity of brain networks in end-stage renal disease (ESRD) patients complicated by frailty. Methods A total of 84 patients with ESRD were enrolled and divided into the frailty group (31 cases) and non-frailty group (53 cases) according to the Chinese version of the Tilburg Frailty Indicator (TFI). Cranial magnetic resonance imaging (MRI) data, neuropsychological test results and clinical data were collected for all subjects. Logistic regression analysis was used to explore risk factors for frailty in ESRD patients, and image preprocessing and independent component analysis were performed to compare differences in brain network functional connectivity between the two groups. Results Logistic regression analysis showed that high blood urea nitrogen level, depression, malnutrition, and sleep disturbance were risk factors for frailty in patients with ESRD (P<0.05), while a higher level of education served as a protective factor (P<0.05). Compared with the non-frailty group, the frailty group exhibited significantly weakened functional connectivity between the sensorimotor network and the visual network (P<0.05). Conclusion High levels of blood urea nitrogen, depression, malnutrition, and sleep disorders can increase the risk of frailty in patients with end-stage renal disease (ESRD), while a higher educational level may reduce this risk. Patients with ESRD complicated by frailty exhibit a significant decrease in functional connectivity between the sensorimotor network (SMN) and visual network (VN), which provides novel imaging evidence for exploring the central neural mechanisms underlying the development of frailty in ESRD patients.