Background The ongoing outbreak of COVID-19 is associated with higher levels of morbidity and mortality among patients with comorbidities, including the metabolic syndrome. Liver impairment has been reported in up to 54% of hospitalized patients with COVID-19. The impact of COVID-19 on a preexisting chronic liver disease is an actively studied area of research. The contribution of our study is towards determining the predictors of severity and the outcome of liver injury among hospitalized patients with COVID-19 infection, including patients with a preexisting liver disease and COVID-19. Methods This single center retrospective cohort study included all patients ≥18 years, admitted in Sheba Medical Center with confirmed COVID-19 infection. Demographic, clinical and laboratory data were obtained using the MDClone platform and rechecked after data decryption using electronic health records. Results Of 382 patients with COVID-19, 66.4% had increased liver biochemistry. Mild increase was observed in 76.7%. The higher level of fibrosis-4 (FIB-4) at admission was independently associated with higher mortality rate. Preexisting liver disease was detected in 15.4% patients. Most common etiology was nonalcoholic fatty liver disease (78.7%). The mortality of hospitalized patients with preexisting liver disease was 16.7% compared to 6.8% in patients without preexisting liver disease (RR = 2.792, P = 0.01). In multivariate analysis, liver disease adjusted to age and BMI was associated with mortality with high statistical significance. Conclusions Patients with preexisting chronic liver disease were at a higher risk of mortality. The FIB-4 level at admission was associated with worse prognosis. These findings should be reevaluated in a larger cohort of patients.