Background Since the beginning of the COVID-19 pandemic, the number of medical appointments and the offer and use of oral health services have decreased sharply with the lockdown period. Restriction to regular dental care can increase the risk of oral diseases, capable of affecting general health and oral health-related quality of life, particularly among medically compromised patients. This study aimed to assess health-related quality of life (HRQoL) and oral health-related quality of life (OHRQoL) of patients with non-alcoholic liver disease (NAFLD) before and during the COVID-19 pandemic. Material and Methods Prospective cohort of 58 patients with NAFLD followed up from March 2020 (before the pandemic) to December 2021 (during the pandemic). RAND 36-Item Health Survey and Oral Health Impact Profile 14 (OHIP-14) questionnaires were used to assess HRQoL and OHRQoL, respectively, in the two points of time. Results The scores of all scales HRQoL and of the question about health change in the last year decreased substantially with the advent of the pandemic. Large (>0.50) effect sizes were estimated for the scales Role functioning/physical, Pain, General health, and Energy/fatigue. Patients who had COVID-19 presented better HRQoL and OHIP-14 mean scores than those who did not have the disease. The OHIP-14 total score increased 3.6 points with the advent of the pandemic, representing a large effect size (0.62). Patients presented high probability (84.3%) of increasing OHIP14 score during the pandemic. Conclusions The HRQoL and the OHRQoL scores of NAFLD patients decreased substantially with the advent of the pandemic. However, these decreases were not associated with the COVID-19 disease by itself, but probably to other factors related to the deep social changes brought by the social isolation measures to combat the pandemic. Key words: Non-alcoholic fatty liver disease, health-related quality of life, oral health, COVID-19.