Flu prevented Phil Jones from travelling with the squad, while Chris Smalling is only fit enough to make the bench, so the experienced centre-back will come in at San Mames
Chris Smalling is likely to make the bench after failing to fully recover from a head injury and, with Phil Jones ruled out with flu, Ferdinand is set to start alongside Jonny Evans in defence.
Anderson is also sidelined with a hamstring injury as United look to overturn a 3-2 deficit from the first leg at Old Trafford last week.
"Jones went down with flu yesterday," Sir Alex confirmed to United's official website.
"Ando [Anderson] could be out for four or five weeks due to his hamstring. Some hamstrings are relatively straightforward but we have to wait and see how he is in the next week or so to get a better idea of where we stand with him."
Manchester United are 27/20 with Sportingbet to emerge victorious away to Athletic.
Ferguson concedes that his side face a tough task in Spain but has pointed to United's away form in Europe this term as a catalyst for their progression.
"It's a difficult tie for us. Bilbao have a tremendous advantage after winning at Old Trafford. It's a challenge but not one that is beyond us," he said.
"Our record away from home helps us - we've done very well. We're going to need a good performance."
How do you stay up to date with football when on the move? With http://m.goal.com – your best source for mobile coverage of the beautiful game.