Arsene Wenger has confirmed Kieran Gibbs will miss tomorrow's encounter at Old Trafford through injury, giving the club a real dilemma at left-back.
It will mean Andre Santos keeps his place in the side, but this will provide cold comfort for Arsenal fans who have been left concerned by his recent performances, and now he faces arguably the best right-winger in the Premier League.
If he can emerge from the game with credit, it could just be the making of him as an Arsenal player, but it also has the potential to do the opposite if the Ecuadorian exposes his defensive flaws.
For all Santos' attacking qualities, defensively his game is poor, as was exposed in the home defeat against Schalke last month in the Champions League.
Gibbs' latest injury came at a bad time for the player, as he was in excellent form, an underrated player in Arsenal's back line, and he had just been called into the England squad.
Santos was rested in the week against Reading, with a view to keeping him fresh for this match up. He will need to be.
Valencia has provided four assists in his last four Premier League starts, and linked up well in the last match at Stamford Bridge to set up former Arsenal man Robin van Persie for his goal.
Santos has onbly made two league starts this season, against Norwich and QPR, but this will be a whole different type of test.
While he may prove a good outlet going forward, he is likely to have his hands full defensively, and will have to get his positioning spot on if he is not to be overly exposed. Arsenal will have to ensure they provide him with good support on the left hand side, and enable him to double up on Valencia, who also has Rafael in tandem who likes to bomb forward.
Stopping Van Persie and Rooney scoring will be tough, and if Santos cannot cut off Valencia's supply line, then it could be decisive.
Arsenal do have other options, but it would mean playing a centre-back out of position, something Thomas Vermaelen has done in the past, but is not particularly comfortable with, and an outside bet is Laurent Koscielny could be asked to do a job, but either way, this is a real weak spot for the Gunners which they will have a tough job mastering for 90 minutes.
Does the prospect Santos v Valencia make Arsenal fans nervous? Can the Brazilian come out on top?
image: © Ronnie Macdonald