Fernandes is serving a one-game European ban due to the red card that he was handed in the clash with Porto last time out.
Man United will also be without Jonny Evans, with the experienced centre-back unable to train on Wednesday morning due to the knock that he suffered during Saturday's 2-1 win over Brentford in the Premier League.
There had been concerns over Matthijs de Ligt and Casemiro, with both players picking up knocks against Brentford.
However, the duo trained on Wednesday and have been included in the squad, with the Red Devils handed a double boost ahead of what is an important clash against the Turkish giants.
Fernandes, Mainoo among Man United absentees
Kobbie Mainoo, Harry Maguire, Tyrell Malacia, Luke Shaw, Mason Mount and Leny Yoro will also not be involved due to injury.
However, Malacia was able to train with the first team on Wednesday, as he continues his recovery from a long-term knee problem, while Shaw took part in an individual session, with the Englishman making progress in his recovery from a calf issue.
There is a spot in the squad for teenager Harry Amass, who is an option at left-back, while Habeeb Ogunneye and Ethan Wheatley are also making the trip to Turkey with the 20-time English champions.
Will Ten Hag make changes from the Brentford game?
Manuel Ugarte was a late substitute against Brentford on Saturday, with the midfielder suffering an injury scare while representing Uruguay during the October international break.
The summer arrival could now be in contention for a start against Fenerbahce, while Joshua Zirkzee is another option, with head coach Erik Ten Hag expected to have one eye on Sunday's Premier League clash with West Ham United.
Noussair Mazraoui, meanwhile, could start, with the Morocco international a late substitute against Brentford after recovering quickly from a minor heart procedure.
Alejandro Garnacho and Rasmus Hojlund both scored against Brentford, while Marcus Rashford put in an improved performance, but Amad Diallo is an option should Ten Hag wish to freshen his attack.
Man United have picked up two points from their two European matches this season to sit 21st in the Europa League table, while Jose Mourinho's Fenerbahce are 13th, claiming four points from their opening two games.
Man United's squad vs. Fenerbahce
Goalkeepers: Altay Bayindir, Tom Heaton, Andre Onana
Defenders: Harry Amass, Diogo Dalot, Matthijs de Ligt, Victor Lindelof, Lisandro Martinez, Noussair Mazraoui, Habeeb Ogunneye
Midfielders: Casemiro, Christian Eriksen, Manuel Ugarte
Forwards: Amad Diallo, Antony, Alejandro Garnacho, Rasmus Hojlund, Marcus Rashford, Ethan Wheatley, Joshua Zirkzee