Arsene Wenger confirmed in his weekly press conference that Welbeck’s knee injury would prevent the forward from playing at Old Trafford.
Welbeck, who joined Arsenal in a £16m move from United in the summer, was expected to play some part after recovering from the problem which forced him to miss Arsenal’s recent games against Hull and Swansea.
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But Wenger said he will be without the man who scored Arsenal’s winner in an FA Cup win away at United in March.
Arsenal are also missing Mikel Arteta and Alex Oxlade-Chamberlain from midfield and Mathieu Debuchy from defence as they prepare to take on Louis van Gaal's side.
However, Aaron Ramsey, who has been playing at right midfield of late, could make it after struggling with a persistent groin injury.
Wenger said Oxlade-Chamberlain had a chance of featuring in the season-ending FA Cup final against Aston Villa if he plays against West Brom on the final day of the Premier League season.
Arsenal have come up short in their league campaign this season and a defeat to United at Old Trafford would see Van Gaal's men usurp them in fourth place.
But Wenger hopes a positive result at the home of an old enemy will set Arsenal up well for next season.
"To win at Old Trafford again would convince us that we have the strength and help us be stronger next season," he said.
"We feel we have made progress. Only one thing shows you have made progress and that's the continuity in your performances."
Welbeck's injury gives Wenger one less selection issue to ponder. There was a half-decent case for putting Welbeck in and hoping that the curse of the ex would strike again, just as it did in the FA Cup. Olivier Giroud's form has also tailed off a touch and a change in attack might have been welcome. But given Welbeck has scored a measly four goals in 25 league appearances this season, it would have been a gamble.
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