Jamal Lewis and Federico Fernandez are both definitely unavailable for the game, with Lewis suffering with a hamstring injury, whilst Fernandez is still trying to regain fitness after recovering from COVID-19.
Additionally, Jamaal Lascelles and Paul Dummett are also doubtful, with Lascelles currently nursing a hamstring injury and Dummett still working his way back after a series of long-term injuries.
However, Bruce also confirmed that Ciaran Clark is also a doubt as his partner went into labour and could be unavailable for the game.
As a result of these injuries, Newcastle might have to drop Isaac Hayden back to centre-half, whilst Matt Ritchie is set to play at left-back to fill in the gap left by Lewis and Dummett.
Speaking on the injuries, Bruce said: "The captain is not going to make it, Ciaran's partner has gone into labour, Dummett is struggling and Jamal Lewis has an injury."
Despite these injuries, Bruce has no problem with selecting Matt Ritchie in the team, despite almost moving to former club AFC Bournemouth on deadline day.
He said "You don't have to question Matt with his professionalism."
"You get to a certain stage in your career and you want to play but I can't guarantee him a place, that's how he almost went to Bournemouth."
Bruce also confirmed that Joe Willock will be involved in the game, after the young midfielder arrived from Arsenal on loan.
"He will be involved. He's young and enthusiastic and raring to go. He will give us that youthfulness that sometimes you need."
"We have been a little bit samey, he will bring a freshness to us."
Newcastle are set to face Southampton on Saturday, with the Saints themselves having plenty of players out injured, and they also have Alex Jankewitz suspended after his horrific debut red card against Manchester United.