We aimed to explore the relationship between sleep quality and frailty, and depression as a mediator and its interaction with sleep quality on frailty. This was a cross-sectional study among 936 Chinese community-dwelling adults aged≥60 years. Sleep quality, frailty and depression were measured by the Pittsburgh Sleep Quality Index (PSQI), the Frailty Phenotype and the 5-item Geriatric Depression Scale (GDS-5), respectively. We found that depression mediated the association between poor sleep quality and physical frailty, attenuating the association between poor sleep and physical frailty by 51.9%. Older adults with both poor sleep quality and depression had higher risk of frailty than those with poor sleep quality or depression alone. These results implicate multidisciplinary care for frail older adults with poor sleep quality.