The Ecuadorian international missed the Red Devils' trip to Turf Moor as they registered a 2-0 victory over Burnley last Sunday. He also missed two league fixtures against Everton and Sunderland, with fatigue being cited as the reason.
According to ESPN FC, the 31-year-old will return to action to face Pep Guardiola's side as United push for a place in the top four. He featured in his side's 2-0 victory over Chelsea, a clash that was sandwiched between the two legs of the Europa League quarter-final clash against Anderlecht.
United progressed to the last four of the Europa League and Valencia played the full 120 minutes against the Belgium outfit in the second leg. The fear of burning out forced Mourinho to drop him from the squad to face Burnley. United have a tough run of fixtures in the final month of the season where they face Celta Vigo in the semi-final of the Europa League.
In addition, they face City, Arsenal and Tottenham Hotspur in the next four league fixtures. ESPN FC's report suggests United are set to manage Valencia's work load carefully from now until the end of the season as the 20-time English champions are fighting on two fronts to secure a place in next season's Champions League.
Meanwhile, Ander Herrera was left hobbling in the end against Burnley after taking a heavy knock on his ankle. He was not the only midfielder who was struggling at Turf Moor as Paul Pogba fell on the pitch and was replaced by Michael Carrick in the stoppage time.
Mourinho admitted he was unsure if the France international would be fit in time to face City. However, the same report claims Herrera is expected to shake off an ankle knock, while United remain positive that Pogba could feature against the Citizens for the midweek derby clash.
Chris Smalling, Phil Jones, Juan Mata, along with Marcos Rojo and Zlatan Ibrahimovic remain long-term absentees. These five players will miss the clash against Guardiola's men on Thursday.
United's clash against City is important for both sides in their quest to finish the season in top four. The Red Devils are currently fifth in the table with 63 points from 32 games, trailing fourth place City by a point. Liverpool are third in the table with 66 points and have played two more games than the two Manchester clubs.