Matip injured his knee during the second half of Liverpool's 4-3 victory over Fulham at Anfield on Sunday - a result that lifted Jurgen Klopp's side a point above Manchester City into second place and two points behind leaders Arsenal.
"I don't know the exact timescale but it doesn't look good," Klopp said of Matip's condition.
"That is something we can say.
"The scan is not done yet so we don't know exactly but it is not great. From the first minute, it was clear.
"I spoke to him and said: 'Ah no, that is not good.' But how long (he will be injured for), we don't know."
On top of that full back Andy Robertson is still recovering from shoulder surgery, midfielder Stefan Bajcetic has suffered a succession of setbacks since returning from an adductor injury and Thiago Alcantara has not played a minute all season.
With a packed fixture list ahead it is hardly ideal although a trip to Sheffield United should not pose too many problems, even if they did reappoint former fan favourite Chris Wilder as manager on Tuesday after sacking Paul Heckingbottom.
"First thing, we can probably bin our analysis!" Klopp said after the managerial change at Bramall Lane.
"We have to focus on ourselves, I don't think he (Wilder) will change too much - what can he change in that short period?
"He probably has his press conference now, training after that and maybe another session in the morning."
"He is right up there. A player with his numbers I'm not sure I will ever coach again," Klopp said.
"His development as a man is incredible and very impressive, as a player as well.
"All-time great, without a shadow of a doubt."