Chris Smalling is only fit enough to make the bench and, with Phil Jones not travelling, Sir Alex has revealed Ferdinand and Jonny Evans will form the heart of the defence. Rafael is set to start at right-back.
Jones has 'flu while Anderson also faces a spell on the sidelines after picking up a fresh injury soon after returning to action.
"Jones went down with 'flu yesterday," said Sir Alex. "Ando 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 [in terms of recovery]."
Athletic Club's energy in the first leg impressed the manager but he feels the 3-2 deficit is far from unassailable.
"It's a difficult tie for us," the boss continued. "Bilbao have a tremendous advantage after winning at Old Trafford. It's a challenge but not one that is beyond us.
"Our record away from home helps us - we've done very well. We're going to need a good performance."