Because the game falls outside the Test window, English-based players will not be available until Wales' second fixture against South Africa a week later.
That means first five-eighths Dan Biggar and Callum Sheedy, wing Louis Rees-Zammit and No8 Taulupe Faletau won't be available.
And because of longer-term injuries, flanker Justin Tipuric, fullback Leigh Halfpenny and wing George North are also unlikely to play.
Interest in the game is high as 20,000 tickets were sold during the first hour of public sales.
Welsh Rugby's chief executive Steve Phillips told The Rugby Paper, "There has been something missing and we will be delighted to welcome fans back for a series which will see many of the superstars of world rugby in Cardiff. A pack-out series will be symbolic of things returning to normal in Welsh rugby."
The first five-eighths duties are likely to be contested by Jarrod Evans, who played against Argentina for Wales in the July internationals, or Rhys Priestland, who last played Test rugby in 2017.
In the loose forwards with Faletau out, Aaron Wainwright is expected to feature, while Ross Moriarty is also likely to be included in the side, with Josh Navidi playing on the openside flank.
Another prospect could be Gareth Anscombe, 30, who has recovered from two knee operations. He is expected to be available for Ospreys when the domestic season starts.
Anscombe, who signed with Ospreys in 2019, has yet to play his first game for the side.
An Ospreys official told The Rugby Paper at the weekend, "Gareth's knee is fine, and the medics expect him to be fit for the start of the new season in the middle of next month.
"He's in good nick and he says he can't wait to get back out there and start enjoying himself."
However, Anscombe faces a tough task in reclaiming Test status as 28 Tests have been played in his absence.