The west Londoners have slipped to the bottom of the table, though can call on January recruit Konstantinos Mitroglou, while Nemanja Vidic returns from suspension for the hosts
The reigning champions lost their eighth game in the Premier League this term at Stoke City last Saturday, and will be looking to get back to winning ways against the west Londoners, who are rooted to the foot of the table.
David Moyes' men currently sit in seventh place and their latest setback leaves them trailing fourth-placed Liverpool by seven points with 14 top-flight matches remaining.
In the latest development of an eventful for season at helm for Moyes, Nemanja Vidic this week revealed he will leave the club at the end of the season.
Vidic returns from suspension this weekend as United strive to avoid a defeat that would equal the most games they have lost in a single Premier League campaign, and leave their hopes of qualifying for Europe's elite competition via league position in further doubt.
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Indeed, the only time Fulham have left Old Trafford with a maximum haul in the Premier League came in a 3-1 triumph in October 2003, with Lee Clark, Steed Malbranque and Junichi Inamoto scoring on that occasion.
United forward Wayne Rooney has enjoyed playing Fulham in the past, with five goals in his last six games across all competitions against the Craven Cottage outfit.
Strike partner Robin van Persie will also be confident of scoring, the Dutchman has six goals in his last seven Premier League outings, including two from two since his return from a month-long lay-off with a groin injury.
United will be without Jonny Evans (calf), Marouane Fellaini (groin) and Nani (hamstring), but Phil Jones (concussion) could feature.
For Fulham head coach Meulensteen, meanwhile, the fixture represents a first return to Old Trafford after being axed as part of Moyes' backroom clear-out, with the Dutchman enjoying spells as part of Alex Ferguson's coaching staff.
But he returns to Manchester with his side in awful form that has seen the side slip to the foot of the Premier League.
Fulham have lost four consecutive top-flight matches including a comprehensive 3-0 setback to Southampton at Craven Cottage in their last league outing.
Morale was further hindered following a 1-0 defeat to Sheffield United in an FA Cup fourth-round replay on Tuesday, with Shaun Miller grabbing the winner in the last minute of extra time.
Club record signing Konstantinos Mitroglou could make his Fulham debut at Old Trafford after being ineligible to face Southampton and Sheffield United.
Defender John Heitinga is also in contention to make his bow following his move from Everton.