Giovanni Leoni is facing a year on the sidelines after Liverpool boss Arne Slot announced the teenage defender has torn his anterior cruciate ligament.
The 18-year-old, a £26million (€29.8m) summer signing from Parma, made his Reds debut in Tuesday's Carabao Cup third round tie against Southampton but suffered the knee injury in a tackle late on in the 2-1 win.
Leoni has pledged to return as soon as possible but Slot issued a grim prognosis ahead of Saturday's trip to Crystal Palace, where Alexander Isak is poised for his first Premier League start for the Merseysiders.
Leoni's setback - which leaves Liverpool with just three fit centre-backs in Virgil van Dijk, Joe Gomez and Ibrahima Konate - means he has been replaced in their Champions League squad by Federico Chiesa.
Slot said: "He is not in a good place because he tore his ACL so he will be out for around a year.
"Being so young, coming to a new country, playing so well in your first game, it is very hard to take a positive.
"There is no positive side but he is still so young, has so many years to go after he recovers from a terrible injury like that."
