The Gunners boss could elect to start January arrivals Leandro Trossard and Jakib Kiwior at the Etihad while resting a host of key stars.
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Arteta fielded a weakened team for the north London outfit's 3-0 victory over Oxford in the third round earlier this month.
But he knows his side will be up against a different machine in City, who they face for the first time this season.
However with Arsenal sitting top of the Premier League table - five points ahead of the Citizens - Arteta will be cautious about selecting too many of his top players.
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And Friday's fixture will give him the perfect opportunity to rotate his starting XI to give a number of squad members invaluable game time.
Though fans should still expect an Arsenal team fully capable of dumping out Pep Guardiola's men in what is the standout tie of the fourth round.
Here is how Arsenal could line up against City in what promises to be an enthralling FA Cup fixture.
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Matt Turner could replace Aaron Ramsdale between the sticks with the American goalkeeper preferred in cup competitions this season.
And there may be changes in the full-back positions too, with Takehiro Tomiyasu coming in for Ben White at right-back.
Kieran Tierney would then feature on the opposite side at the expense of Oleksandr Zinchenko, who will be returning to City for the first since since his move to Arsenal last summer.
William Saliba could keep his place in the side, where he may partner Polish star Kiwior in the heart of defence.
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A £22million arrival from Spezia, the left-footed centre-back has been labelled as 'extraordinary' by international teammate Robert Lewandowski.
Arteta then has a decision to make over who to start as his defensive midfielder between Thomas Partey and Albert Sambi Lokonga.
And the Spaniard could opt for Partey as he knows winning the midfield battle will be prove decisive against City.
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Granit Xhaka would then be deployed in his usual No.8 free-roaming role, with Fabio Vieira coming in for club captain Martin Odegaard.
Just as he did against Oxford, Saka will likely start on the right wing, with Trossard to be handed his first start on the opposite flank ahead of Gabriel Martienli.
The £27m signing from Brighton impressed in his cameo off the bench in Sunday's epic 3-2 win against Manchester United.
And with Arsenal having no other established centre-forward in their ranks with Gabriel Jesus out injured, Eddie Nketiah will once again be the man tasked with leading the line.
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