Cazorla has not played for Arsenal since October 2016 and has undergone eight operations on a troublesome Achilles issue.
The 32-year-old revealed earlier in November that he was told the injury might have left him unable to walk before travelling to his native Spain for further surgery.
Wenger had initially planned to welcome the former Malaga man back into his squad at the turn of the year and remains hopeful that could still be the case.
"It is the worst injury (I have known)," the Gunners boss said. "It started with a pain in the Achilles and it has gone from worse to worse and I must say I know how much Santi loves to play football and loves to be out there every day and I feel very sorry for what happened to him, because it is unbelievable.
"I saw him one month ago, he was here, and I told him to prepare as well as he can.
"He has competent medical people around him and he tries to practice, but I have not spoken to him recently but I hope he comes back. I left him out of the squad, hoping he would be available in January."
When it was put to Wenger if there were doubts over whether Cazorla would ever play again, the Frenchman replied: "Let's not talk about that, but I hope you are wrong."