Sean Longstaff has suffered an ankle injury in training, while Andy Carroll is close to a return for Newcastle, says head coach Steve Bruce.
Longstaff has played in all four Premier League games so far this season after recovering from a knee injury which kept him out of the final stages of the last campaign.
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The 21-year-old attracted interest from Manchester United in the summer following his impressive performances in his breakthrough season, but Bruce confirmed he has been sidelined due to an injury in training.
Bruce said: “Unfortunately, Sean Longstaff turned an ankle yesterday in training. He won’t make tomorrow.
“He tried to block a cross and unfortunately twisted his ankle and we won’t know how severe that is until the next couple of days. That’s a bit of a blow to us.
“It’s one of those freak ones which unfortunately happens. We were disappointed for him that we’ve lost a player to a freak accident. That’s what happens in football unfortunately.”
Newcastle started the season poorly with defeats against Arsenal and Norwich, but rallied to pick up a shock win at Tottenham thanks to record-signing Joelinton’s goal.
The Brazilian striker has not faced much competition for his place in the side yet, however, he could be challenged by Andy Carroll, who is nearing a return after he was re-signed on Deadline Day.
Bruce said: “[Carroll has] made big progress this week. He’s delighted with how it has gone so far. It’s good news for us.
“I think for everybody to see him joining in with training was good for him, good for the group of course and we need now some positive news from his specialist.
“It’s always very difficult to put timescale on someone like Andy, he’s fit when he’s fit. He’s joined in, he’s worked extremely hard, there’s a smile across his face this morning where he’s comfortable which is good.
“When you’ve got an ankle like he’s got, it’s always the reaction to the work he’s put in. At the moment it’s all very good.”
Newcastle face a trip to Premier League leaders Liverpool on Saturday as they look to be the first team to collect points from Jurgen Klopp’s side this season, and Bruce admits it will be a very tough challenge.
He added: “We’re going to European champions who haven’t lost a game at home for two and a half years.
“They are as good a team as you’re ever going to play against so we’ll have to defend well that’s for sure. But we need to take part in the game and show that resilience like we did against Spurs.
“When we’ve got it, can we cause a threat and that’s got to be the game plan straight away again.
“It’s a great stadium with a great support, a big club, big history, big tradition. To go there and play against them is for me always going to be one of the highlights because they are quite unique in what they’ve done over the years in their history.
“I’ve always just enjoyed it. In the big games it’s important that you just enjoy it, that’s what were in it for. It couldn’t be anymore difficult because they’re a very, very good team now.”