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De Bruyne has been absent since injuring his knee against Fulham at the start of November.
He has made just two starts all season having injured his other knee in training last August.
Aguero has missed the last four games with a muscle injury.
John Stones has a slight knock but is available to face his former club and Fernandinho has also shaken off a minor injury.
All three start on the bench.
Ederson, Walker, Otamendi, Laporte, Delph, Fernandinho (c), Gundogan, Mahrez, Sane, Bernardo, G Jesus
Subs: Muric, Sterling, Stones, De Bruyne, Aguero, Foden, Zinchenko
In attack, expect the Blues to have Riyad Mahrez on the right flank, Leroy Sane on the left and Gabriel Jesus in the centre.
Behind those three are likely to be skipper Fernandinho, Ilkay Gundogan and Bernardo Silva.
Nicolas Otamendi and Aymeric Laporte resume their central defensive partnership, flanked by full-backs Kyle Walker and Fabian Delph
Pep Guardiola understandably doesn’t want to pitch Aguero and De Bruyne straight into the thick of the action today, but we may see cameo roles from the duo depending how the game is going.
Raheem Sterling is given a rest – to begin with – but is likely to feature at some stage.
City have the chance to return to pole position in the Premier League this afternoon and put the ball firmly back in Liverpool’s court ahead of their clash with United tomorrow afternoon.
Jose Mourinho has had a number of successes at Anfield over the years and City will know that three points against Everton will add more pressure on Jurgen Klopp’s side to respond.
But the Toffees have proved a tough nut for City over the years, particularly on home soil.
Pep is yet to taste a home Premier League win against the Merseysiders with the two previous home games ending in draws.
Today would be a great time to end that run.
Since the 2017 thrashing at Goodison Park, City have gone 51 games unbeaten against sides that have started the day outside the top six in the table.
Everton’s last win at the Etihad was in 2010.
Aguero is two shy of 250 career goals – but has just two goals in 12 against the Toffees – his worst ratio for any of the 31 top flight sides he’s faced.
Pep has beaten Marco Silva in all five games he’s faced against the Portuguese as a manager.
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