Fletcher did not take part in the section of training which was open to cameras at Carrington earlier on Tuesday, and while Scholes had been involved in the session, neither was included in the squad list for the trip to Portugal posted on United's website on Tuesday afternoon.
Fellow midfielder Nick Powell appeared to have sat out on Tuesday morning but was included in the list, along with defender Chris Smalling, who has been making progress in training in his rehabilitation from a broken metatarsal and may be in line for his first appearance of the season in Wednesday's game.
Phil Jones (back and knee), Nemanja Vidic and Shinji Kagawa (both knee) all miss out.
Douglao (thigh) returned to action at the weekend after missing Braga's last three matches in all competitions.
But Paulo Vinicius, Ismaily, Paulo Cesar, Carlao and Djamal were all sidelined through injury.