Manchester City forward Mario Balotelli is losing his battle to recover from a knee injury.
Midfielder Nigel de Jong is rated as 50-50 as he struggles to overcome an ankle injury.
Manchester United
Injured: Ferdinand (calf), Hargreaves (hamstring), Valencia (ankle)
Manchester City
Doubtful: Balotelli (knee), De Jong (ankle)
Injured: A Johnson (ankle), Richards (concussion)
MATCH PREVIEW
It's 43 years since Manchester City were last crowned champions of England; how Sir Alex Ferguson's United would revel in trying City's patience with victory at Old Trafford on Saturday.
You have got to earn the title. Nobody gives you the trophy. The team that wins the league will be the team that deserved it and showed the best form throughout the season
Man Utd's Darren Fletcher
The Red Devils' invincible aura has been shattered, but they remain on course for a record 19th league title. A win in this fixture would see them open up a seven-point lead at the top of the Premier League table and surely do irreparable damage to City's dreams of a first league title since 1968.
City head to Old Trafford seeking to prove they are ready to compete on equal terms. The Eastlands club this week closed the gap on their rival's lofty position in the European money league, but it is the Premier League title that matters most to Roberto Mancini's side.
Last season's league clash at Old Trafford was described by Ferguson as "probably the best derby of all time" after Michael Owen's 96th-minute winner settled an extraordinary contest in United's favour. Ferguson delighted in silencing his "noisy neighbour" back then and will relish the chance to remind City that it is United who remain Manchester's top dog.
MATCH FACTS
Head-to-head
• Manchester City have won just one of their last 26 league visits to Old Trafford.
• The Eastlands club have failed to score in four of the last five league encounters with United.
• The two sides have drawn 49 of their 143 league encounters.
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Manchester United
• Man Utd have earned 37 points out of a possible 39 at Old Trafford this season, 10 more than the next best home record.
• Sir Alex Ferguson's side have not conceded a first-half goal at Old Trafford in the Premier League since April 2010.
• According to Opta Stats, United have scored the most headed goals in the Premier League this season (14). But they have also conceded the highest percentage of headed goals in the top flight (33%).
Manchester City
• City have not lost any of the 25 league games in which Carlos Tevez has scored, winning 23 of them.
• The Argentine has scored four goals in his last six appearances against former club United in all competitions.
• Only Arsenal (25) have earned more points away from home in the Premier League than City (22) this season, but they are winless in their last three on the road.
LEADING GOALSCORERS
Manchester United
Berbatov: 20 goals (19 league); Hernandez: 11 goals (7 league)
Manchester City
Tevez: 20 goals (18 league); Balotelli: 8 goals (5 league)
MATCH OFFICIALS
Referee: Andre Marriner
Assistant referees: Adam Watts & Scott Ledger
Fourth official: Martin Atkinson
LAST LEAGUE MATCH LINE-UPS
Manchester United (L1-2 v Wolves, a): Van der Sar; Rafael, Evans (Smalling 65), Vidic, Evra, Nani, Fletcher, Carrick (Scholes 46), Giggs, Berbatov (Hernandez 65), Rooney. Subs not used: Kuszczak, Owen, Anderson, O'Shea.
Manchester City (W3-0 v West Brom, h): Hart; Boateng, Kompany, Toure, Kolarov, Zabaleta, Toure Yaya (Dzeko 63), Barry, Milner, Tevez (Wright-Phillips 86), Silva (Razak 90). Subs not used: Given, Lescott, Vieira, Jo.
Source: BBC Sport
Source: BBC Sport