Box-to-box midfielder Lee has a knee issue following months out with a hip problem while centre-forward Hooper is still laid low by a groin problem.
Lee and Hooper have not made a senior appearance for the Owls since last December.Â
Manager Jos Luhukay told The Star: "I think these two players will not play again for us this year.
"They have had treatment in the last weeks and months but they are not on the field.
"They are not training with the sports science staff. It is only physio work they are doing.
"Kieran has been out over a year. Gary has been out since December.
"They are not training outside with the sports scientists or the team and it is now the middle of October."
Lee and Hooper's recoveries appeared to be going in the right direction when they played in aÂ Wednesday Under-23 fixture last month. However,Â Lee lasted only 16 minutes and Hooper was withdrawn at half-time against Colchester United.
Luhukay, whose team go to 16th-placed Queens Park Rangers tomorrow, added: "Hopefully they can come back to training sessions and training with our team but they have been out such a long time.
"I don't think they will come back to our team in November or December.
"Hopefully Gary and Kieran will come back to the team in January."