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Objectives: The novel coronavirus disease (COVID-19) pandemic has led to social distancing measures and impaired medical care of chronic neurological diseases, including epilepsy, which may have adversely affected well-being and quality of life of patients with epilepsy (PWE). The objective of this study is to evaluate the impact of the COVID-19 pandemic in the levels of anxiety, depression, somnolence, and quality of life using validated scales in PWE in real-life clinical practice., Materials & Methods: Self-administered scales of anxiety disorders (GAD-7), depression (NDDI-E), somnolence (Epworth Sleepiness Scale; ESS), and quality of life (QOLIE-31-P) in PWE treated in a Refractory Epilepsy Unit were longitudinally analyzed. Data were collected before the beginning (December 2019 - March 2020) and during the COVID-19 pandemic (September 2020-January 2021)., Results: 158 patients (85 from the first round and 73 from the second round) 45.0 ± 17.3 years of age, 43.2% women, epilepsy duration 23.0 ± 14.9 years, number of antiepileptic drugs 2.1 ± 1.4, completed the survey. Significant longitudinal reduction of QOLIE-31-P (from 58.9 ± 19.7 to 56.2 ± 16.2, p = .035) and GAD-7 scores (from 8.8 ± 6.2 to 8.3 ± 5.9, corrected p = .024) was identified. No statistically significant longitudinal changes in the number of seizures (from 0.9 ± 1.9 to 2.5 ± 6.2, p = .125) or NDDI-E scores (from 12.3 ± 4.3 to 13.4 ± 4.4, p = .065) were found. Significant longitudinal increase of ESS (from 4.9 ± 3.7 to 7.4 ± 4.9, p = .001) was found., Conclusions: During the COVID-19 pandemic, quality of life and anxiety levels were lower in PWE, and sleepiness levels were raised, without seizure change., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)