In December 2019, pneumonia of unknown aetiology in China was identified and later characterized as a new coronavirus (World Health Organization, 2020a). Severe acute respiratory syndrome 2 (SARS-CoV-2) became known for its high transmissibility and potential infection due to its pathogenicity that can cause coronavirus disease-2019 (COVID-19). COVID-19 manifests in different clinical outcomes and may present signs and symptoms developed in a mild, moderate, severe, or critical form (Deng, 2020; Wang et al., 2020; Wang, Tang, & Wei, 2020). In January 2020, the World Health Organization declared COVID-19 a public health emergency of international interest and, in March, a pandemic (World Health Organization, 2020b, 2020c). Patients with liver cirrhosis, who are in an immunodeficiency state, can be more susceptible to SARS-CoV-2 infection (Irvine, Ratnasekera, Powell, & Hume, 2019; Marjot et al., 2020). When infected with the virus, diverse evidence indicates that people with liver cirrhosis have worse clinical outcomes, with increased hepatic decompensation and increased hospitalization and death risks (Marjot et al., 2020; Singh & Khan, 2020). The objective of this study was to prepare and validate the content of a guideline for the nursing care of adult patients with liver cirrhosis and COVID-19 treated in the emergency department. The study was conducted in two stages: first, the guideline was developed based on an integrative literature review and existing guidelines on the topic. The guideline was prepared with six domains and 64 care items. In the second stage, 15 specialists in urgency and emergency services performed content validation of the guideline. The data were analyzed using the Content Validity Index, with reliability assessed through Cronbach’s α. The judges validated the guide regarding language clarity, objectivity, theoretical relevance, and practical pertinence. The value of the guideline’s Content Validity Index was 0.96. Cronbach’s α reliability reached a value of 0.93. The judges validated all domains and items of the guideline for theoretical relevance and practical pertinence to be used by researchers and clinical practice professionals in the nursing area.