•Liver transplantation patients faced unique challenges during the pandemic.•Challenges included dependence, fear, and stress.•Coping strategies included establishing a support network and reorganizing demands.•Patients demonstrated determination to create strategies to prevent SARS-CoV-2.•This data may inform better preparation by professionals involved in patient care. We aimed to identify the challenges and strategies experienced by patients undergoing liver transplantation during the COVID-19 pandemic. This was a descriptive study with a qualitative approach conducted in a large liver transplant hospital in southern Brazil. The participants included liver transplant patients between the years 2011 and 2022. Data collection was performed using a semi-structured interview. Data analysis comprised approximation of information and calculation of percentages. A total of 23 patients participated. Challenges identified included an increased dependence on others for daily activities, fear and stress due to the possibility of contamination, and the need for isolation from family and friends. Strategies included adaptation to the daily routine, reorganization of tasks inside and outside the home, formation of a support network, and reduced attendance to consultations and exams. Evidence of anguish and suffering of patients facing isolation and separation from family members was observed. Still, the study revealed the strength and determination of the patients to create strategies for preventing the SARS-CoV-2 virus and caring for themselves and their families. The study demonstrates the need for support from the health team in the face of such a scenario.