SARS-CoV-2 shares nearly 80% of its' genomic sequence with SARS-CoV and MERS-CoV, both viruses known to cause respiratory symptoms and liver impairment. The emergence of pediatric cases of multisystem inflammatory syndrome related to the SARS-CoV-2 infection (PIM-TS) has raised concerns over the issue of hepatic damage and liver enzyme elevation in the critically ill pediatric population with COVID-19. Some retrospective cohorts and case series have shown various degrees of ALT/AST elevation in SARS-CoV-2 infections. A limited number of liver histopathological studies are available that show focal hepatic periportal necrosis. This liver damage was associated with higher levels of inflammatory markers, C-reactive protein (CRP), and pro-calcitonin. Proposed pathophysiological mechanisms include an uncontrolled exacerbated inflammatory response, drug-induced liver injury, direct viral infection and damage to cholangiocytes, hypoxic-ischemic lesions, and micro-thrombosis in the liver. Based on the physiopathological characteristics described, our group proposes a clinical protocol for the surveillance, evaluation, management, and follow-up of critically ill pediatric COVID-19 patients with liver damage.