The German coach has rotated heavily in La Liga so far, using three different combinations across the first four games. Ronald Araujo, the vice-captain who takes the armband in Marc-Andre ter Stegen's absence, started alongside Pau Cubarsi in the opening two fixtures but did not feature in the last two.
Araujo missed the 6-0 win over Valencia, and Spanish reports suggested his omission was tactical. Flick is believed to have rested him to keep him fresh for Newcastle, where the aerial threat will be far greater.
The Magpies will line up with summer signing Nick Woltemade, the towering German striker who stands at six feet six inches. Flick has hinted that physicality will play a major role in his selection. "Every opponent has strengths. Newcastle are a very physical side and we must be ready to compete in those duels," the Barcelona coach has said.
Few defenders in Europe relish that kind of battle more than Araujo. Despite Barcelona's struggles in the Champions League in recent years, he remains their most imposing defender when fully fit. Real Madrid forward Vinicius Junior once described him as "the footballer who has defended me the best. He is very good and very strong, that's why he plays for Barca."
Alongside him, 18-year-old Cubarsi looks likely to keep his place after an outstanding display against Valencia, where he impressed both in defence and in building from the back. Andreas Christensen, with his Premier League experience at Chelsea, is another option Flick may consider.
For Araujo, the trip to St James' Park represents more than just a group-stage match. The Uruguayan has been directly involved in Barcelona's last two Champions League eliminations, and this will be an opportunity to prove his worth on one of Europe's toughest stages.
"The Champions League is always a different challenge," Flick has said. "We need leaders on the pitch, and every decision we make has that in mind."
All eyes will now be on whether Araujo and Cubarsi can handle the Newcastle test and give Barcelona the defensive solidity they have been searching for under Flick.
Erling Haaland has hailed Gianluigi Donnarumma's debut after the Italian goalkeeper played a key role in Manchester City's 3-0 win over Manchester United at the Etihad on Sunday.
Nigeria forward Ademola Lookman is set to be excluded from Atalanta's squad for the opening Champions League fixture of the season against Paris Saint-Germain.
Harry Kane has insisted that Bayern Munich will not simply cruise to another Bundesliga title, despite many tipping them to dominate German football again this season.
Borussia Dortmund head coach Nico Kovac has urged his players to deliver a statement performance when they face Juventus in the Champions League league phase on Tuesday night in Turin.
