Hugo Ekitike was left in visible pain after a collision with James Milner just minutes into Liverpool's 2-1 defeat to Brighton.
After receiving medical treatment on the pitch, he attempted to continue but quickly signalled to the bench that he was unable to play on.
The forward left the field in tears with only eight minutes played, prompting an early tactical change from Slot.
With no other natural striker on the bench, the Liverpool boss brought on Curtis Jones, hoping to form a dynamic attack alongside Cody Gakpo, Dominik Szoboszlai, and Florian Wirtz.
However, the makeshift frontline struggled to create clear-cut chances, and a lack of clinical finishing contributed to the Reds' second league defeat in three matches as they head into the international break without a win.
Slot offers Ekitike injury update
After the game, Slot highlighted how Ekitike's absence had significantly weakened his side.
"Of course, it was a big blow for us that one of the two strikers we have available is already not here [Alexander Isak] and then the other one [Ekitike] has to go off," Slot told TNT Sports.
"That’s usually not helpful, especially when you look at how well Hugo played on Wednesday [against Galatasaray in the Champions League]."
When initially asked about the injury, Slot described it as "bad enough not to be able to continue." He sympathised with the player's emotional reaction, explaining the high stakes of the season's final stretch.
"I think the players, the fans know there were only eight games to go to qualify for the Champions League, and then every game you have to miss is something you’re upset about," he said.
"Him having to go off... is a big blow for him and in the end a big blow for us."
Liverpool will be hoping to have at least one of their main strikers fit for their crucial FA Cup quarter-final against Manchester City on April 4. This is followed by a Champions League quarter-final first leg against Paris Saint-Germain on April 8.