There was tension between the clubs last month when City midfielder Owen Hargreaves questioned the medical treatment he had received during his injury-ravaged years at United.
He is now fit and has a chance to feature against his former club with much to prove.
Aguero, who came off the bench to score in the 2-1 triumph over Villarreal on Tuesday, could return to the starting lineup while Mario Balotelli may be preferred to Edin Dzeko up front after the Bosnian wasted several chances against the Spaniards.
United should have captain Nemanja Vidic back for his first league game since August following a calf injury. The Serb was sent off in the midweek 2-0 win at Romanians Otelul Galati.
Away from Manchester, third-placed Chelsea make the short trip to neighbours Queens Park Rangers on Sunday (2030 IST) looking to gain ground on the pacesetters.
Arsenal look to build on last week's win over Sunderland that lifted them into the top half of the table when they host Stoke City on Sunday (1800 IST).
Newcastle United, in fourth, seek to maintain their unbeaten start at home to Wigan Athletic on Saturday (1930 IST).
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