It has been reported that Anderson is set to miss the remainder of the campaign with a hamstring injury, although as yet, there has been no official confirmation from the Old Trafford outfit.
Sir Alex Ferguson confirmed Nani had sat out Sunday's Premier League win over West Brom with "bruising" suffered during a training-ground knock, but the United boss pointedly avoided responding to an inquiry about the reason for Anderson's absence.
The return of Valencia is good news, though, with the winger having been in impressive form until he suffered a hamstring injury in Amsterdam four weeks ago.
As United have since assumed top spot in the Premier League, Ferguson is keen to have as many men as possible available for the run-in.
The Red Devils' 20-man travelling squad included teenager Paul Pogba, surely a further sign that the young French midfielder is ready to spurn the offer of a lucrative contract from Juventus.
Paul Scholes was there too, although whether the veteran starts is open to debate given United are 3-2 down after the home leg and face a trip to Wolves on Sunday in the Premier League.
Under the circumstances, there are plenty who think the game in Bilbao is one worth sacrificing, although Ashley Young is not one of them, even if United have never recovered from a home first-leg deficit in a European knockout game.
"It is unusual that we find ourselves in this position but there is a great team spirit here and everyone is full of confidence," the winger said. "Our form in general makes us believe we can score wherever we play.
"Our attacking play has been fantastic of late and we believe we can score the two goals we need."
On the two occasions they have attempted a comeback away from Old Trafford, against Bayern Munich in 2001 and AC Milan four years later, they have lost the away leg as well.
Indeed, it is a measure of the task United are facing that it is five seasons since they overturned a first leg deficit on home soil. That 7-1 annihilation of Roma has gone down in Red Devils folklore and victory on Thursday will achieve similar status.
"Our focus has not changed from the start of the season," Young said. "We want to win every competition we enter and the Europa League is no different. Bilbao were an impressive team last week.
"They were a very attacking team, had a good team shape and at times we found them hard to break down, but I am sure if we are on our game 100% we can go there and get the win we need."
As Ferguson noted last week, winning is one thing, doing it by two goals quite another. That is what United are likely to need though given the high-scoring nature of the first-leg, when Wayne Rooney scored twice, part of his overall 26-goal tally.
Not that Young has done too badly lately, bagging an impressive double in the win at Tottenham, then winning the penalty Rooney converted against West Brom at the weekend.
"It is nice to be contributing," he said. "As a winger you are there to get assists and goals and that is what I have been doing. Fingers crossed it can continue and we can keep winning."