The striker has missed City's last four matches due to a knee injury and Pep Guardiola planned to check on his fitness on Friday afternoon.
If City win at the Etihad, they will become the earliest title winners in the history of the Premier League.
However, they come into the encounter on the back of a 3-0 defeat to Liverpool in the first leg of their Champions League quarter-final, and may have one eye on the return leg next Tuesday.
United were eliminated at the last-16 stage of the Champions League, but have otherwise been in good form recently, with five wins from their last six games in all competitions.
"My motivation is to finish second," said United manager Jose Mourinho. "I still have the motivation of finishing top four because mathematically it is not done, so that's the first objective.
"And because we are in the second position for many, many, many, many months, obviously it is our objective to fight for that and for that we need points."
Aside from the doubts over Aguero, City's only other absentee is Benjamin Mendy.
United are only missing back-up goalkeeper Sergio Romero after he was involved in a collision on Argentina duty.
Matej Kovar, 17, was brought into first-team training on the eve of the derby as Kieran O'Hara is set to play in the reserves on Friday.
Versatile Daley Blind is back in contention for United, while Phil Jones, Marcos Rojo and Ander Herrera have also recently returned to full fitness.
Manchester City have done the double three times over Manchester United in the Premier League, only Liverpool have done so more often in the competition (4).
Manchester United have lost eight of their last 13 Premier League games against Man City (W3 D2) - their previous eight top-flight defeats against Man City came over a 49-game period stretching back to March 1978.
Man City are unbeaten in their last 27 home league games (W22 D5), winning the last 14 in a row. Only twice has a team ever had a longer winning run at home in the Premier League (Man City 20 between March 2011 and March 2012, and Man Utd 19 between October 2010 and October 2011).
United have only won one of their last 10 away league games against fellow 'big six' sides (D3 L6), failing to score on eight occasions in that run.
Manchester City have won 27 league games so far this season - their record for most wins in a single top-flight season is 28 in 2011-12 campaign. They had to wait until Matchday 38 for their 28th and final win that season.
This will be the 21st managerial meeting between Jose Mourinho and Pep Guardiola, the most either manager has faced another. Guardiola has won nine of the previous 20.
I expect Man City to win. If you could say to Man United a 0-0 draw, I think they'd chop your arm off. I think United will turn up and play for a 0-0, but I just don't see City not breaking them down before 90 minutes is up. United won't play the way Liverpool play, they haven't got the legs to do that all around the pitch.
City's confidence will be shot. They will have lost a lot of confidence from that Liverpool loss - no shot on target in 90 minutes, the way they've been playing.
The only team that can upset City are Liverpool, because they're the only side that plays that way against City. I think other teams are scared, they go into games against City and show too much respect, but Liverpool's success starts from the front three - they've got pace and close down properly.
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