Both clubs finished as runners-up in their respective leagues last season, but have made promising starts in the view of going one better.
Match preview
Under Adi Hutter, all signs are pointing in the right direction for Monaco, after only finishing second to Paris Saint-Germain in Ligue 1 last season.
An unbeaten start was extended to four games with a 3-0 win over Auxerre at the weekend, allowing Hutter to make multiple substitutions ahead of this encounter with the game wrapped up after an hour.
This will be a huge step up from the opponents they have been facing domestically though, putting that unbeaten start in danger.
With Barcelona first up, Monaco will also welcome Benfica and Aston Villa to the principality, while making trips to Inter Milan and Arsenal in what is set to be a challenging league phase for them.
Even though their upcoming opponents may be a daunting prospect, Monaco's record against Spanish clubs could give them great confidence, having won seven of their previous nine.
A dismal recent run of home form in this competition is cause for concern though, having lost seven in a row at the Stade Louis II - no side has ever lost eight home games in a row in the competition's history.
Hutter will hope much has changed in terms of the mentality since their last appearance in the competition back in 2018 then, which ended in a second consecutive group stage exit.
The club do have a fantastic record in the Champions League overall though, considering they have only qualified for it on nine occasions, reaching one final, three semi-finals and a quarter-final.
They have only met Barcelona in one previous campaign, back in 1993, when the Catalonian side won both meetings without conceding.
Hansi Flick's side will look to make that three from three as they gear up for a 21st consecutive season in Europe's top-tier competition, but for the stature of the club, they must improve on their recent showings.
Since becoming European champions in 2015, Barca have only progressed beyond the quarter-finals once, a run which includes two group stage exits in 2021 and 2022.
That is in stark contrast to the record they had during the club's glory years, reaching at least the semi-finals 10 times in 15 campaigns between 1999 and 2015.
Monaco may not be the ideal opening opponents either, considering Barca have won on just two of their last nine visits to France, one of which was at PSG last season before losing the quarter-final tie anyway.
The Blaugrana are often fast starters though, especially in recent campaigns, putting five past Ferencvaros, Viktoria Plzen and Antwerp in opening-day victories across the last four seasons.
A blistering league start will also fill the handful of Culers making the short trip to southern France with confidence, as Sunday's 4-1 win over Girona extended their 100% start to five matches, scoring 17 goals in the process, with Lamine Yamal stealing the show once again with two of them.
Monaco form (all competitions):
L
W
W
W
D
W
Barcelona form (all competitions):
L
W
W
W
W
W
Team News
Monaco should be able to call upon midfielder Lamine Camara as Ligue 1 have validated his release from concussion protocols after being stretchered off with a neck injury against Auxerre at the weekend.
The two confirmed absentees remain Edan Diop and backup goalkeeper Radoslaw Majecki, who will not be available for selection until next month at the earliest.
Hutter made eight changes to his side for the clash with Lens before the international break, but reverted back to the same XI which had beaten Lyon for the Auxerre game at the weekend, so with many players at his disposal, more changes could be incoming.
Barcelona have been left disappointed by the news that Dani Olmo will be out until after the October international break with a hamstring injury sustained against Girona on Sunday, leaving Flick extremely short on midfield options.
Olmo joins a very long list of absentees at Barca, with Fermin Lopez, Gavi, Frenkie de Jong and Andreas Christensen among those also out.
Ronald Araujo is currently sidelined with a hamstring injury, but he would have been suspended anyway after his red card against PSG in last season's quarter-final.
Robert Lewandowski has scored eight Champions League goals since joining Barca, taking his tally overall to 94, and he will be setting his sights on becoming the third player to hit the century mark during this league phase.
Monaco possible starting lineup:
Kohn; Vanderson, Kehrer, Mawissa Elebi, Caio Henrique; Camara, Zakaria; Akliouche, Minamino, Ben Seghir; Embolo
Barcelona possible starting lineup:
Ter Stegen; Kounde, Pau Cubarsi, Inigo Martinez, Balde; Eric Garcia, Pedri, Casado; Lamine Yamal, Lewandowski, Raphinha
We say: Monaco 0-2 Barcelona
While an all-time unwanted home losing record awaits Monaco if they suffer defeat here, the form of Barcelona does look concerning for them despite their injury concerns.