Fabregas suffered a recurrence of his hamstring problem during Arsenal's 3-1 midweek defeat to Barcelona in the UEFA Champions League.
The Spanish midfielder only started the clash at Camp Nou after passing a late fitness test on his hamstring.
However, after the game Fabregas revealed that he aggravated the injury just 15 minutes into the match, but played on with the problem.
It is unsure how long Fabregas faces on the sidelines with the new problem, but the injury is a major blow to Arsenal's hopes of success in the FA Cup and Premier League.
Fabregas is joined on the sidelines by goalkeeper Wojciech Szczesny after he suffered a dislocated finger against Barcelona.
Szczesny sustained the problem during the first half of Tuesday night's second leg meeting at Camp Nou after collecting a free-kick from Dani Alves and was forced off in just the 19th minute.
Forgotten man Manuel Almunia replaced him against Barcelona and it looks like the Spaniard is set for an extended run in the side with Lukasz Fabianski already ruled out for the rest of the season.
Wenger has admitted he is looking to bring in an emergency goalkeeper to help provide cover for the injured Szczesny and Fabianski.
Better news on the injury front for Arsenal is that striker Robin van Persie is available to play after suffering no reaction to playing following a knee injury.
Van Persie, who was controversially sent-off against Barcelona, is set to lead the line at Old Trafford as Arsenal look to bounce back from their Champions League exit.