Alexander Isak is expected to be out of action for two months after fracturing his leg against Tottenham, with Liverpool manager Arne Slot accusing Tottenham's Micky van de Ven of making a "reckless challenge".
The Sweden striker was injured in a tackle from the defender in the act of scoring the opening goal in Saturday's 2-1 victory and limped off the pitch.
Liverpool said in a statement on Monday that the forward had had an operation on an ankle injury that included a fibula fracture.
"It's going to be a long injury, for a couple of months," Slot told reporters on Tuesday, "So, yeah, that's a big, big, big disappointment for him. And as a result also of course for us."
Slot described Van de Ven's tackle as "reckless".
"I think I said a lot about the tackle of Xavi Simons (sent off earlier in the game for Spurs), which for me was completely unintentional, and I don't think you will ever get an injury out of a tackle like that.
"The tackle of Van de Ven, if you make that tackle 10 times, I think 10 times there's a serious chance that a player gets a serious injury."
Isak's injury is the latest setback for the forward after he signed from Newcastle for a British record £125 million ($168 million) in September.
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A dispute with Newcastle meant he did not have a proper pre-season programme and arrived at Liverpool well behind his teammates in terms of fitness.
His season was then interrupted by a groin injury.
The 26-year-old has scored just three goals in 16 appearances since completing his protracted move to Anfield.
Isak's absence will be a major blow for Reds boss Slot, with Mohamed Salah at the Africa Cup of Nations and Cody Gakpo not ready to return from a muscle injury until early in the new year.
🗣️ Arne Slot provides an update on how long Alexander Isak will be out of action for... pic.twitter.com/sc6aDFyjaj
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It leaves Slot with Hugo Ekitike, who has five goals in his past four games, and the little-used Federico Chiesa as his only senior forwards.
Liverpool, whose Premier League title defence collapsed after a shocking run of results, have climbed to fifth in the table after extending their unbeaten league run to five games.
Isak's injury raises the prospect of Liverpool moving to boost their attack in the January transfer window, with Bournemouth winger Antoine Semenyo linked with a move to Anfield.
It may also change the conversation around Salah, who had been linked with a move to Saudi Arabia following his recent claim that he had been thrown under the bus by the club and no longer had a relationship with Slot.
Salah's rant, which came after he was left on the bench for three successive matches, prompted Liverpool to leave him out of the squad for a Champions League match at Inter Milan.
But he returned to action as a substitute against Brighton before leaving for international duty.
Liverpool host bottom side Wolves on Saturday.