Objective: In early 2020, Italy struggled with an unprecedented health emergency related to the COVID-19 pandemic. Medical care of chronic neurological diseases, such as epilepsy, is being sorely neglected. In this national survey, we aimed at understanding the impact of COVID-19 lockdown on the care of people with epilepsy (PwE) and identifying PwE risk factors for seizure worsening to direct telemedicine efforts. Methods: We administered a 48-items online survey (published on April 11, 2020) including socio-demographic, epilepsy-related, and psychometric variables (BDI-II for depression, GAD-7 for anxiety, and PSQI for sleep) to PwE and people without epilepsy (PwoE). Regression analysis identified predictors of seizure worsening. Results: We collected responses from 456 PwE (344 females) and 472 PwoE (347 females). Outpatient examinations of PwE were postponed in 95% of cases. One-third of PwE complained of issues with epilepsy management, but only 71% of them reached the treating physician and solved their problems. PwE had worse depressive and anxiety symptoms (higher BDI-II and GAD-7 scores; p < 0.001) than PwoE. Sleep quality was equally compromised in both groups (47 and 42%). Sixty-seven PwE (18%) reported seizure worsening, which was best explained by the number of anti-seizure medications (ASM) of chronic therapy and the severity of sleep disorder. Conclusions: During the current COVID-19 pandemic, a significant percentage of PwE experienced difficulties in follow-up and a seizure number increase, in particular those chronically taking more ASMs and with poor sleep quality. This dramatic experience outlines the urgent need for validation and implementation of telemedicine services for epileptic patients in order to provide regular follow-up.