The Argentine has made just 14 appearances in the last 12 months, with his most recent start coming at the end of February in our win over West Ham.
With the game against Fulham coming just three days after our win over Southampton – and with a Champions League last-16 game to play in Budapest on Tuesday – Pep Guardiola has made seven changes to his starting XI.
Along with Aguero, in come Joao Cancelo, Benjamin Mendy, John Stones, Rodrigo, Ferran Torres and Gabriel Jesus.
Kyle Walker, Oleksandr Zinchenko, Kevin De Bruyne, Fernandinho, Ilkay Gundogan, Riyad Mahrez and Phil Foden all make way.
Ederson, Aymeric Laporte, Ruben Dias and Bernardo Silva are the only four to keep their place.
Nathan Ake isn’t yet fit enough to return to the squad after his recent injury troubles, and Raheem Sterling is rested.
XI: Areola, Tete, Andersen, Loftus-Cheek, Adarabioyo, Cavaleiro, Lemina, Lookman, Reed, Abguissa, Aina
Subs: Fabri, Hector, Ream, Kongolo, Bryan, Robinson, Onomah, Maja, Mitrovic
XI: Ederson, Cancelo, Stones, Dias, Laporte, Mendy, Rodrigo, Bernardo, Torres, Jesus, Aguero
Subs: Steffen, Walker, Gundogan, Zinchenko, De Bruyne, Fernandinho, Mahrez, Foden, Garcia
It would appear City are set to lineup with a 3-5-2 system – a deviation from our usual 4-3-3.
A back three of John Stones, Ruben Dias and Aymeric Laporte will offer protection in front of Ederson, with Joao Cancelo and Benjamin Mendy given licence to attack in wing-back roles.
Rodrigo will sit deep and play the defensive-midfield role, with Bernardo Silva and Ferran Torres just ahead of him.
And Gabriel Jesus and Sergio Aguero look set to play in tandem in a two-man strike force.
It's an intriguing selection, and with Guardiola's propensity to surprise, it could be something completely different!
One thing is for sure: it will be fluid, with City intent on dominating possession and playing on the front foot.
Fulham have lost 10 consecutive matches against Manchester City in all competitions and are winless in 16 since a 3-1 Premier League victory at Etihad Stadium in April 2009.
City have scored in each of our past 26 meetings, winning the last six by an aggregate score of 18-0.
City are on a club record run of 12 consecutive away victories in all competitions.
Pep Guardiola's side can equal the club record of 16 successive competitive away matches unbeaten, set from January to September 1999.
We have won 22 of our past 23 league and cup games.
We have dropped points in only two of our 15 league matches so far this season against teams currently in the bottom half of the table: 1-1 draws with Leeds and West Brom.
Ilkay Gündogan has scored 10 of his 12 Premier League goals this season in 2021.
Guardiola has won all five competitive matches as a manager against Fulham by an aggregate score of 13-0.