Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a significant threat to global public health. Despite reports of liver injury during viral disease, the occurrence and detailed mechanisms underlying the development of secondary exogenous liver injury, particularly in relation to changes in metabolic enzymes, remain to be fully elucidated. Therefore, this study was aimed to investigate the mechanisms underlying SARS-CoV-2-induced molecular alterations in hepatic metabolism and the consequent secondary liver injury resulting from alcohol exposure. We investigated the potential effects of SARS-CoV-2 infection on alcohol-induced liver injury in Keratin 18 promoter-human angiotensin converting enzyme 2 (K18-hACE2) transgenic mice. Mice were intranasally infected with 1 × 10