The Magpies host Ralph Hasenhüttl's side at St. James' Park (kick-off 3pm GMT), aiming to end a winless run of five league matches on home soil.
Bruce revealed, however, he could be faced with a number of defensive absentees this weekend, with centre-back pair Jamaal Lascelles and Federico Fernández ruled out to face the Saints.
"Defensively, it's a concern," Bruce explained. "Jamaal Lascelles and Federico Fernández will not make it. Ciaran Clark's partner has gone into labour so we're hoping he'll still make it.
"We have a worry to Jamal Lewis, who has a hamstring problem, and Paul Dummett is still struggling so that defensive part of the team is a bit depleted at the minute."
Bruce hinted new signing Joe Willock, who joined Newcastle on loan from Arsenal on Deadline Day, could be in contention to make his United debut against Southampton.
The Magpies head coach is hopeful the 21-year-old midfielder, who made his Premier League bow at St. James' Park for the Gunners in April 2018, will prove to be a beneficial factor to the squad for the duration of the league campaign.
"He'll be involved,"Bruce added. "He's been training with us for two or three days.
"He's a little bit different to what we've got. He wants to get forward and score a goal - that's in his locker - and he's got the ability to get up and down the pitch. He's young, enthusiastic and raring to go.
"He'll hopefully give us that youthfulness which, at times, you need. We're delighted to get him and he'll bring a bit of freshness to our midfield.
Southampton suffered a humiliating 9-0 thrashing against Manchester United at Old Trafford in midweek and have been dealt with a host of injury issues in recent weeks.
Bruce, who captained the Red Devils to the first ever 9-0 victory in the Premier League against Ipswich Town in 1995, expects the majority of the Saints' first-team players to return to competitive action ahead of their trip to Tyneside as United bid to bounce back from Tuesday's 2-1 home defeat to Crystal Palace.
"As far as Southampton is concerned going into the game, the one thing I'm sure the manager will want is some of his big players to be fit," he said. "It looks as if they are and they overturned the decision of the red card for (Jan) Bednarek so they could be near enough back to full strength from being depleted the other night.
"He looks as if he's got that and he'll be looking for a reaction. We have to stick to what we're doing and I've been very pleased. We didn't get the result the other night but I was pleased with a large part of the game. We have to keep that momentum going.
"We had 20 attempts and 60% possession (against Crystal Palace) which pleased me. The numbers of chances we created pleased me too but unfortunately we gave away poor goals away and that 15-20 minutes ultimately cost us."
After DeAndre Yedlin's transfer to Galatasaray on Monday freed up a spot in the club's 25-man Premier League squad, Bruce also confirmed that winger Christian Atsu has taken the American defender's place.
"Christian Atsu comes back into it," Bruce said. "There was only him or (Henri) Saivet to choose from, so it was pretty straightforward."
