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Manchester United's draw at Leeds last weekend leaves Man City 10 points clear at the top of the table with five games remaining, meaning two more wins would confirm them as champions.
It has been a busy few days for City with Sunday's Carabao Cup final win over Tottenham followed by Wednesday's thrilling 2-1 Champions League comeback victory at Paris Saint-Germain.
Guardiola largely stuck with the same players in both games, and has changed things up ahead of next week's vital semi-final second leg against PSG.
Raheem Sterling and Gabriel Jesus come into the attack, joining Sergio Aguero in a front three.
City have no real injury concerns, though Ilkay Gundogan was lucky to escape following a horror challenge by Idrissa Gueye in midweek.
Gundogan avoided a potentially serious calf injury and is on the bench at Selhurst Park with Fernandinho coming in.
John Stones is out as he serves the second game of a three-match suspension for his red card at Aston Villa, with Aymeric Laporte returning after his Carabao Cup final winner.
Crystal Palace XI: Guaita, Ward, Kouyate, Dann, Mitchell, Riedewald, Milivojevic, Eze, Townsend, Benteke, Zaha Subs: Butland, Van Aanholt, Ayew, Mateta, Schlupp, McCarthy, Batshuayi, Cahill, Kelly
Manchester City XI: Ederson, Joao Cancelo, Laporte, Ake, Mendy, Torres, Rodri, Fernandinho, Sterling, Aguero, Jesus Subs: Walker, Dias, Gundogan, Zinchenko, Steffen, De Bruyne, Bernardo, Mahrez, Foden