The 58-year-old revealed the midfielder - who made his Premier League bow at Anfield in December - will not travel with the squad to Merseyside after the 21-year-old suffered an ankle injury in training.
And ahead of this weekend's meeting with Jurgen Klopp's Reds (kick-off 12.30pm BST), Longstaff joins a handful of squad members ruled out through injury, with Andy Carroll, Allan Saint-Maximin, Matt Ritchie and Dwight Gayle all sidelined for the Magpies.
"Unfortunately, Sean Longstaff turned an ankle yesterday in training so won't be in contention on Saturday," Bruce said. "It's one of those freak injuries where he has tried to block a cross. We'll not know how severe this is until the next couple of days but it's a bit of a blow of us.
"It's still a bit early for Andy Carroll and Allan Saint-Maximin, but they've made big progress this week. Andy is away to see a specialist this afternoon and, touch wood, he's delighted with how it has gone so far which is good news for us.
"With Allan, we are bordering on the air of caution after what happened last time with him so another seven days before we play Brighton next week. Hopefully, he will be in contention for then.
"Matt Ritchie has been quite remarkable in his recovery. He's shocked us all. We weren't expecting to see him for at least a couple of months. The way he trained yesterday and the day before - as long he doesn't have any reaction - then I don't think he's very far away so that's good news to us.
"With Dwight Gayle, we have gave him complete rest and hope that is the key to it. It's a frustrating one for everyone. For Dwight, he gets to a certain level and unfortunately keeps feeling it. We hope in the next few weeks that after complete rest, he's going to be ok.
Liverpool, who lifted the European Cup last term, sit top of the Premier League after winning their opening four league games, with Newcastle aiming to record a first league win at Anfield since 1994.
However, Bruce is hoping to take positives from United's impressive win against Tottenham three weeks ago in their bid for a positive result against the Reds, despite Liverpool last losing at home in April 2017 and currently boasting a 13-match unbeaten run in the top flight.
He added: "It gave everybody a lift at the right time. We were disappointed with the way we played against Norwich the week before so we needed some sort of response at Spurs. We played very well against Leicester in the cup tie and unfortunately lost on penalties and we did ok against Watford.
"However, we're going to the European champions who haven't lost at home in two and a half years. They're as good a team as you're ever going to play so we'll have to defend well but we need to take part in the game and show that resilience which we had shown against Spurs and when we've got it, can we cause a threat. That's got to be the game plan again.
"A record is always there to be broken. However, they are the European Champions. They are as good as you get so we hope we can catch them on a bit of an off day. Up front they’re as good as I’ve seen, so we’ll have to defend well. It’s always been a big fixture whether you're a player, manager or coach and you want to go there and take them on. It’s what we’re in it for.
"The core of the squad have been together a couple of years and they’re a really honest and genuine group. When you’ve got that, you’re capable of doing anything. They’ve gone to Spurs and won and they beat Man City last year, so they’ve got it in them."
