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The purpose of the study was to evaluate sleep quality in the parents of children with epilepsy (CWE) as well as their symptoms of anxiety and depression in Southern China. A structured questionnaire, comprised of The State–Trait Anxiety Inventory (STAI), Center for Epidemiologic Studies Depression Scale (CES-D), and the Pittsburgh Sleep Quality Index (PSQI), was administered to parents of CWE (n = 234) in Xiangya Hospital and parents of healthy children (n = 230) during 2019–2020. The scores (Mean ± SD) of State Anxiety Inventory (S-AI) and Trait Anxiety Inventory (T-AI) among parents of CWE were 51.850 ± 11.380 and 48.201 ± 9.526, respectively, which were significantly higher than those of control group (37.172 ± 8.047 and 37.478 ± 7.314, respectively) (p < 0.001). Compared with 10.84% in parents of healthy children, 23.51% of parents of CWE had symptoms of depression (p < 0.001). The mean score of total PSQI among parents of CWE (6.944 ± 3.814) was statistically higher than that of parents of healthy children (5.039 ± 3.390) (p < 0.001). Moreover, anxiety and depression subscores among parents of infants with epilepsy were significantly higher than in other groups. The T-AI and CES-D could explain 43.9% of the variance (R2 = 0.444, F = 92.215, p < 0.001) on the PSQI. Our study showed more severe symptoms of anxiety and depression as well as poorer sleep quality among parents of CWE, especially in the infants group. In light of this information, more attention should be paid to early identification and intervention of symptoms of anxiety and depression in susceptible parents who are the main caregivers of their CWE. • Anxiety, depression and poor sleep quality were found in parents of children with epilepsy, especially in the infant group. • Low sleep quality may precede mood disturbance or develop as a result of them. • Greater attention should be paid to the main care taker of sick child with epilepsy. [ABSTRACT FROM AUTHOR]