Objectives. The combination of epilepsy, intellectual disability, and other psychiatric comorbidities disorders represents an extreme burden on their families and lay caregivers. The study aimed to investigate previously missing data on the burden and level of stress lay caregivers of patients with epilepsy and mental/intellectual disability and possible changes during the COVID-19 pandemic. Methods. The unicentric pilot study in lay caregivers of dispensed patients with epilepsy and concurrent mental/intellectual disability in an Epilepsy Center focused on lay caregivers burden. Caregiver burden was subjectively assessed for a period before and during the COVID-19 pandemic using the Caregiver Burden Scale. The Chi-Square Test was used for statistical evaluation at a significance level of 0.05. Results. Since the beginning of the COVID-19 pandemic, 526 patients were dispensed with the principal diagnosis of G40.* in the selected center; 46 lay caregivers were included in the study (9 males, and 37 females; the patient’s average age was 52.1 years). Due to the limitation of respite services, 25 (54.3%) caregivers reported worsening economic situations, and 31 (67.4%) reported increased stress levels. Increased caregiver burden during the COVID-19 pandemic was verified for walking (15 cases, p = 0.001), dressing, and bathing (12 cases, p = 0.010) activities. Conclusion. The obtained results confirmed the high dependency rate of patients and identified several factors (impaired mobility, falls, aggression, fear of COVID-19 disease) that increase the level of burden and stress in their caregivers due to the inability to use respite care and common tools for external assistance in care. Worsening socioeconomic situation and increased use of antidepressants by caregivers have been identified. The analysis also confirmed differences in the availability of respite care by place of residence at the national level.