Sir Alex Ferguson's side need four more points from their remaining three league games to take the crown.
Ferdinand missed Sunday's Manchester derby after picking up a calf strain in training on Saturday.
His replacement Evans limped off with a hamstring injury midway through the 2-0 victory over Manchester City.
If both are injured and O'Shea switches to the centre of defence, Ferguson must choose between Rafael Da Silva or fit-again Gary Neville.
Ferguson is world's best manager - Whelan
Ferdinand, though, is reluctant to return too early, knowing United could secure the Premier League trophy, assuming they beat Wigan, in front of their home fans against Arsenal on Saturday.
"I have won it at away grounds and been in my house when another team has lost, so it would be nice to win it at Old Trafford," he said.
"But in all honesty, I would win it anywhere. I would win it on the grass outside the training ground if I had to."
Wigan's Kirkland and Zaki were injured in Saturday's 3-1 defeat by West Brom.
Last May, Manchester United won this corresponding fixture 0-2 at the JJB, and thus gained the points they needed to retain the Premier League title. Twelve months later, Wigan again entertain a Red Devils outfit, this time in need of four points from the last nine available to claim a second hat-trick of Premier League crowns, and an 11th title in this league.
If United avoid defeat here they could clinch a record-equalling 18th English top-flight championship, home to Arsenal on Saturday or away to Hull on Sunday week.
United have won their last six Premier League games; Wigan are chasing their first win in six.
This is the 150th Premier League game, and 75th at home for the Latics, who are still searching for their first Premier League victory over a member of the 'Big Four'.
The two managers, Steve Bruce and Sir Alex Ferguson, share the same birthday (31 December), but were born 19 years apart. Both were appointed to their current clubs in the same month (November), 21 years apart.
Bruce, who is 48, has never beaten his old boss as a manager. He has drawn two and lost 10 of 12 games against Ferguson's United, when in charge of either Birmingham or Wigan, 11 of those being Premier League games.
Ferguson has only been beaten five times in 55 Premier League matches against clubs managed by one of his former players.
Manchester United have won all eight league and cup matches they have played against Wigan.
Distance between the clubs: 23 miles (37 kilometres)
1. Gained one point out of a last possible 15 from a goalless draw, home to Bolton.
2. Failed to win 13 of their last 15 Premier League matches; failing to score in nine of them.
3. The current total of 42 points after 35 games is six points up on this stage last season. Only maximum points from the last three fixtures would see them equalling their Premier League best points total of 51.
4. Need to score two more goals to total 150 in their Premier League history.
5. Only avoided defeat in four of their 31 matches against the 'Big Four'; Arsenal, Chelsea, Liverpool and Manchester United. The 1-1 draw with Liverpool at the JJB on 28 January is their only point in seven games against the elite quartet this season.
6. Their only victories over top-half clubs this term have been against Everton, Tottenham and Manchester City.
7. Lost home and away to Chelsea, Arsenal and West Ham. Manchester United could become the fourth and last club to do the double over them this season.
8. Scored more than two goals in a home league game once this season (3-0 Blackburn on 13 December) and conceded four goals twice (0-4 to Villa on 26 October, and 1-4 to Arsenal on 11 April).
9. The season concludes after this with a trip to Stoke and a home clash with Portsmouth.
2. Lost two of 24 top-flight matches, and failed to score in one of the last 19. Since losing 2-0, away to Fulham on 21 March, 16 goals have been scored in six outings.
3. This is their 63rd match of the season; more than any other Premier League club. Arsenal have been the second busiest top-flight club this term, having played 59 matches thus far.
4. The current total of 83 points after 35 games is two points up on last season, when they were also top of the table. Maximum points from their last three games would see them amass their highest total in a 20-club Premier League, and equal the 92 points accrued from 42 games in 1993-94.
5. Gone 19 league games since a goalless draw; the last being away to Spurs on 13 December. Also, on the longest current sequence of 27 matches in the Premier League without a score draw; the 1-1 stalemate at Everton on 25 October being the most recent.
6. The only home points dropped this season have been courtesy of defeat to Liverpool (1-4, 14 March), and an early draw with Newcastle (1-1, 17 August).
7. Already done the double over nine clubs; West Ham, Stoke, Bolton, Portsmouth, Blackburn, Sunderland, Middlesbrough, West Brom and Manchester City. Wigan and Hull could still be added to that list.
Edwin VAN DER SAR is leading the race for the Barclays Golden Glove with 20 clean sheets.
Cristiano RONALDO is the highest scoring Premier League player with 26 goals in all club competitions this season.
The 24 year old Portugal international is also the top scorer in the Premier League with 18 goals, leading the race for the Barclays Golden Boot by one from Chelsea's Nicolas ANELKA.
RONALDO has scored seven goals in five starts and two substitute appearances against Wigan (Premier League and Carling Cup final).
Wayne ROONEY, who needs a hat-trick to total 100 goals for Manchester United, has played in all eight of United's league and cup meetings with Wigan and has scored six goals, including the first minute winner in this season's reverse fixture.
Dimitar BERBATOV has scored three goals in five Premier League appearances against Wigan - all in Tottenham colours.
Paul SCHOLES needs a double to reach 100 Premier League goals - all for United.
Ryan GIGGS is a double shy of 150 goals for Manchester United.
Patrice EVRA will be playing two days before turning 28.
Rio FERDINAND will be making his 400th career league appearance (West Ham, Bournemouth, Leeds and Manchester United).
Tomasz KUSZCZAK will be making his 50th career Premier League appearance (West Brom and Manchester United).
HEAD TO HEAD
Manchester United have beaten Wigan in all seven Premier League meetings with an aggregate score of 19-3.
The Latics have conceded more Premier League goals to United than to any other club (19).
This match pits the clubs with the biggest and smallest attendances in the Premier League; United have had 1,355,308 people through the turnstiles and Wigan only 309,674.
Home and away
League (inc PL): Wigan 0 wins, Man United 7, Draws 0
Prem: Wigan 0 wins, Man United 7, Draws 0
at Wigan only
League (inc PL): Wigan 0 wins, Man United 3, Draws 0
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