The Magpies - who have been renowned for their defensive acumen this season - will be forced to cope without both Nick Pope and backup Martin Dubravka for the tie at Wembley.
During Saturday's 2-0 defeat to Liverpool, Pope misjudged a long ball over the top from Alisson Becker - to which Mohamed Salah gave chase - but the Magpies goalkeeper nevertheless tried to beat the Egyptian to the ball.
However, Pope missed his header and inadvertently handled the ball well outside of his area while sprawled on the ground, receiving a straight red card from Anthony Taylor in the process.
Pope had already shipped goals to Darwin Nunez and Cody Gakpo before being given his marching orders, which means that he will be forced to sit out the EFL Cup final through suspension.
Dubravka came on for Elliot Anderson on Saturday evening and proceeded to keep a clean sheet for the rest of the game, but the Slovakia international represented Man United during the earlier rounds of the EFL Cup while on loan at Old Trafford.
The 34-year-old started in the Red Devils' wins over Aston Villa and Burnley in the third and fourth round respectively, and he is therefore cup-tied for the contest.
With Karl Darlow also out on loan at Championship side Hull City and unable to be recalled, Howe is facing a toss-up between Loris Karius or Mark Gillespie for the meeting with Erik ten Hag's men at Wembley.
Karius has not played for an English club since his error-strewn display for Liverpool in the 2017-18 Champions League final, having since spent time on loan with Besiktas and Union Berlin.
The 29-year-old only played five times for the latter in the 2020-21 season before leaving Liverpool as a free agent last year, and he has not made a matchday squad for Newcastle since October.
While Karius is still waiting to make his Newcastle debut, Gillespie played three times for the Magpies in the 2020-21 EFL Cup, but he has not made a first-team appearance for the club since.
The 30-year-old has played once for the Under-21s in the Premier League 2 this season, and Howe believes that the decision to send Pope off was "harsh".
"Nick's very disappointed, he's been magnificent this season and he doesn't deserve to miss next week's game," Howe told the media after the match.
"I think it's harsh, it was a slippy surface and the ball hit his arm; the referee could have given him a yellow card. Nick's visibly upset. But I was really pleased with the way we responded to going down to 10 men."
Newcastle are clinging onto fourth spot in the Premier League table, but they will be knocked out of the Champions League places if Tottenham Hotspur beat West Ham United on Sunday afternoon.