De Bruyne came on as a substitute against Everton last weekend and started in the Carabao Cup in midweek, and Guardiola will have to decided whether to name the Belgian in the starting XI again, or keep him back for away games against Leicester and Southampton after Christmas.
The Catalan will also have to decided between Sergio Aguero, who also returned in midweek, and Gabriel Jesus, who scored twice against Everton a week ago.
Man City injuries
David Silva misses out again with a hamstring injury, while Benjamin Mendy is out following knee surgery.
Vincent Kompany has missed the last two match day squads with an unspecified injury.
Claudio Bravo is a long-term absentee with an Achilles injury but Danilo has returned to training this week following a number of set-backs.
Man City suspensions
Neither side have any suspensions.
Man City potential starting line-up
Oleksandr Zinchenko could start at left-back in place of Fabian Delph, as the Ukrainian has generally started home matches against teams expected to defend. With two tricky away matches coming up, Delph could be kept back.
John Stones has a good chance of partnering Aymeric Laporte at centre-back given Nicolas Otamendi has looked a little shaky of late, and both young centre-backs are especially good on the ball.
Guardiola may be tempted to bring De Bruyne back slowly, and would mean a midfield partnership of Bernardo Silva and Ilkay Gundogan playing ahead of Fernandinho.
Aguero is more likely to return to the starting line-up given he has not been out of action for anywhere near as long as De Bruyne, but Jesus' two goals against Everton could provide him with the opportunity to start in the league yet again.
Raheem Sterling is likely to come back into the line-up after starting the last two matches on the bench, and Leroy Sane could provide the width on the left-hand side as he has tended to do in the absence of Mendy.
Crystal Palace team news
Goalkeeper Wayne Hennessey is out after missing last weekend's win over Leicester, as is defender Martin Kelly.
Cheikhou Kouyate was withdrawn during that game and will be assessed to see whether he can return against City.
Christian Benteke is a long-term absentee with a knee injury.
Opta match facts
- Manchester City have won 10 of their last 12 Premier League matches against Crystal Palace (D1 L1) and are unbeaten in the most recent six clashes (W5 D1).
- Crystal Palace have failed to score in eight of their last 10 Premier League games against Manchester City, netting just three goals in this run.
- Manchester City have won 10 and lost none of their last 13 home games in all competitions versus Crystal Palace (D3), since a 0-2 defeat in December 1990 in the top-flight.
- Since moving to the Etihad Stadium in 2003, only Arsenal (638) and Chelsea (626) have scored more home Premier League goals than Manchester City (615). 21% of those strikes have been since Pep Guardiola took charge (131).
- Manchester City are currently on the longest ever Premier League unbeaten run in games kicking off at 3pm local time on Saturday (W32 D4 L0), winning their last 15 such games by an aggregate score of 57-7.
- Manchester City’s Sergio Aguero has been directly involved in five goals in his last four Premier League games against Crystal Palace (3 goals, 2 assists).
TV coverage & kick-off time
Kick off is 15:00 GMT (10:00 ET) on Saturday. The game will not be shown on television in the United Kingdom. It will be shown on NBC in the United States, and on various channels around the world.