Objective Stress is a known trigger for seizures in patients with epilepsy (PWE). However, the association between stress and seizures has not been thoroughly investigated. In December 2019, an outbreak of coronavirus disease (COVID-19) occurred in Wuhan, Hubei province, China, causing tremendous collateral stress. This study was designed to evaluate the influence of the COVID-19 outbreak on seizures in PWE in the most severely affected area, Wuhan, and its surrounding cities. Methods In this single-center, cross-sectional study, PWE were surveyed via online questionnaires between February 23 and March 5, 2020. Collected data included demographic information, epilepsy-related characteristics (seizure type, frequency, antiepileptic drugs [AEDs], and medication management), direct and perceived threat of COVID-19, and changes in seizures during the outbreak. Psychological comorbidities were evaluated by the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 items, and Insomnia Severity Index (ISI). Multivariate logistic regression was used to identify precipitants for seizure exacerbation. Results We received 362 completed questionnaires after excluding 12 duplicates (response rate = 63.51%). A total of 31 (8.56%) patients had increased seizures during the outbreak. Exposure history to COVID-19 (P = .001), uncontrolled seizure after AED therapy (P = .020), seizure frequency of two or more times per month before the outbreak (P = .005), change of AED regimen during the outbreak (AED reduction, withdrawal, replacement, skipping altogether;P = .002), and worry about the adverse effect of the outbreak on overall seizure-related issues (severity = moderate to critical;P = .038) were risk factors for increased seizures. Significance A minority of PWE experienced seizure exacerbation during the outbreak of COVID-19. Stress, uncontrolled seizures, and inappropriate change in AED regimen were associated with increased seizures. Based on these findings, stress might be an independent precipitant for triggering seizures in some PWE.