Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), first emerging in December 2019 and continuously evolving, poses a considerable challenge worldwide. It was reported in the literature that neonates had mild upper respiratory symptoms and a better outcome after Omicron SARS-CoV-2 variant infection, but there was insufficient data about complications and prognosis.In this paper, we present the clinical and laboratory characteristics of four COVID-19 neonate patients with acute hepatitis during the Omicron SARS-CoV-2 variant wave. All patients had a clear history of Omicron exposure and were infected via contact with confirmed caregivers. Low to moderate fever and respiratory symptoms were the primary clinical manifestations, and all patients had a normal liver function at the initial stage of the course. Then, the fever lasted 2 to 4 days, and it was noted that hepatic dysfunction might have occurred 5 to 8 days after the first onset of fever, mainly characterized by moderate ALT and AST elevation (>3 to 10-fold of upper limit). There were no abnormalities in bilirubin levels, blood ammonia, protein synthesis, lipid metabolism, and coagulation. All the patients received hepatoprotective therapy, and transaminase levels gradually decreased to the normal range after 2 to 3 weeks without other complications.This is the first case series about moderate to severe hepatitis in COVID-19 neonatal patients via horizontal transmission. Besides fever and respiratory symptoms, the clinical doctor should pay much attention to evaluating the risk of liver function injury after SARS-CoV-2 variants infection, which is usually asymptomatic and has a delayed onset.© 2023 Wang, Hu, Wang, Yu, Chang and Rong.