Background:Liver impairment has been reported as a common clinical manifestation in patients with Severe Acute Respiratory Syndrome Coronavirus 2 infection, with varying degrees of severity ranging from a mild elevation of liver enzymes to acute liver failure. However, the prevalence and clinical significance of liver injury in Coronavirus Disease 2019 (COVID-19) patients, particularly in low- and middle-income countries such as Nepal, remains poorly understood. To investigate the hepatic injury related to this disease and its clinical significance, the authors conducted a retrospective study that included adult patients with COVID-19 infection in security hospitals of Nepal.Methodology:The authors performed a retrospective chart review on 1007 COVID-19-positive patients who underwent a liver function test during their admission in two COVID-19 dedicated hospitals in Nepal from April 2021 to January 2022. The data were collected and entered into Microsoft Excel before being exported to SPSS version 24 for analysis. Univariate and multivariate logistic regression were used to determine factors associated with liver injury. We reported adjusted odds ratios (aOR) with 95% CI.Results:Of the total, 549 (54.5%) patients had an acute liver injury. Among 549 patients, 68.1% were mild, 27.9% were moderate, and 5.0% were severe. Out of 1007 patients, 1.4% had cholestatic liver injury. Most patients with mild, moderate, and severe liver injury had greater than or equal to 10 C-reactive proteins (CRP). In multivariate logistic regression, sex, and CRP were significantly associated with the presence of liver injury. Males had 1.78 times higher odds of having a liver injury compared to females (aOR:1.78; 95% CI: 1.37–2.30,P-value:<0.001). Similarly, patients who had CRP greater than 10 had higher odds of having liver injury compared to those who had CRP less than 10 (aOR: 1.84; 95% CI: 1.41–2.39;P-value: <0.001).Conclusions:The present study reveals that COVID-19 infection is commonly associated with mild increased liver enzymes. However, the likelihood of developing acute liver injury was found to be higher in patients with an inflammatory state indicated by CRP levels greater than 10. Furthermore, the study highlights the sex-based difference in the prevalence of liver injury, with males demonstrating a higher predisposition.