Rosacea is a chronic facial skin disease involved in neurovascular dysregulation and neurogenic inflammation. Behavioral factors such as stress, anxiety, depression and sleep were identified to be associated with other inflammatory skin diseases. Few studies have reported sleep status in rosacea. Aiming to investigate the relationship between rosacea and sleep, a case-control survey was conducted, enrolling 608 rosacea patients and 608 sex- and age-matched healthy controls. Sleep quality was assessed through the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Diagnosis and severity grading of rosacea were evaluated under the standard guidelines of the National Rosacea Society. More rosacea patients (52.3%, n=318) suffered poor sleep quality (PSQI, >5) than the healthy controls (24.0%, n=146), displaying a much higher PSQI score (rosacea vs control, 6.20 vs 3.95). There was a strong association between sleep quality and rosacea (odds ratio [OR], 3.525; 95% confidence interval [CI], 2.759-4.519). Moreover, the severity of rosacea was also associated with sleep quality (OR, 1.847; 95% CI, 1.332-2.570). Single nucleotide polymorphisms in hydroxytryptamine receptor 2A and adrenoceptor-β1 genes, which are associated with sleep behaviour, were detected and revealed to be associated with rosacea. Furthermore, the LL-37-induced rosacea-like phenotype and sleep-deprivation mice models were applied, revealing that sleep deprivation aggravated the rosacea-like phenotype in mice, with higher expression of matrix metallopeptidase 9, Toll-like receptor 2, cathelicidin antimicrobial peptide and vascular endothelial growth factor. In conclusion, rosacea patients presented poorersleep quality, as well as a higher propability ofgenetic background with sleep disturbance. In addition, poor sleep might aggravate rosaceathrough regulating inflammatory factors, contributing to a vicious cycle in the progression of disease.