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The Argentine, who has scored 13 goals in his last 14 games, was withdrawn during injury time of the 2-2 draw with Middlesbrough last weekend after suffering a groin injury and has failed to recover in time to face Sam Allardyce’s resurgent side.
Goalkeeper Claudio Bravo, who damaged his calf in the recent draw with Manchester United, is also out, with manager Pep Guardiola admitting he is unlikely to play again this season, and John Stones has also failed to recover from his abductor problem.
The good news for Guardiola is that David Silva is back in full training, however, he remains doubtful for the game against the Eagles.
“No [Aguero is not fit],” Guardiola said. “Hopefully next one but this game no.
“Yesterday was the first training session [Silva completed since injury]. The action from the semi-final in the FA Cup, he is still not perfect.
“Claudio out until next season and John maybe in the next games [he will return].”
With four games of the season still to play, City remain locked in a battle to finish inside the top four and qualify for next season’s Champions League.
Of those four matches, three are at home – but City have performed better on the road this season than they have at the Etihad Stadium.
But Guardiola says he is confident his side can get the job done and ensure they take their place in Europe's elite competition for the seventh successive year.
“It is still in our hands,” he said. “We will see if we can make a step forward and qualify.
“If we win all four games, we will definitely be in the Champions League, maybe in the third position.
“It depends on us. Our home games were not perfect in the season and we have to change it if we want to play in Europe next season.”
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