Background: Social factors are believed to affect mental health in patients with epilepsy (PWE). However, there is still a lack of sufficient manifest proof, given the difficulty of exposing PWE to relatively consis-tent natural social environments with a low or high level of social interaction to study their significant role. Methods: This single-center, longitudinal study was conducted via online questionnaires during the coro-navirus disease 2019. PWE were recruited from downtown Wuhan and surrounding areas. The Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 were used to assess psychological status. Results: We analyzed 588 questionnaires completed by 294 PWE who participated in the dual survey. Under lockdown and reopening, the prevalence of anxiety was 13.6%/22.5%, and the prevalence of depres-sion was 19.4%/34.0%. Raising children and seizure-related characteristics, including uncontrolled sei-zures, seizure exacerbation, seizure frequency > 2/m, and changes in drug regimen, were risk factors in the first and second surveys. A high education level (OR =1.946, 95% CI = 1.191-3.182), low life satis-faction (OR =1.940, 95% CI = 1.007-3.737), worry about unanticipated seizures (OR = 2.147, 95% CI = 1.049-4.309), and worry about purchasing medication outside (OR = 2.063, 95% CI = 1.060-4.016) were risk factors for higher scores after reopening. Worry about unanticipated seizures (OR = 3.012, 95% CI = 1.302-6.965) and in-person medical consultation (OR = 2.319, 95% CI = 1.262-4.261) were related to newly diagnosed patients with psychological disorder after reopening. Conclusions: We identified an associatin between social variables and epileptic psychiatric comorbidities. (c) 2021 Elsevier Inc. All rights reserved.