The 27-year-old was not able to train with his national side on Monday or Tuesday due to "muscle complaints", and he has now been ruled out of the clash with Stephen Kenny's team.
However, Santos is expecting the Manchester City attacker to be available for Sunday's clash with Serbia, which could potentially decide which team tops Group A.
"I don't count on him (Silva). He has muscle complaints. I don't think he has the conditions to go to this game. We think he will be okay for Serbia," Santos told reporters.
"He arrived tired, complaining, he has many games on him, and couldn't go to training, but he's recovering well and we hope and we believe he'll be able to play here with Serbia."
Portugal, who have won their last five matches in all competitions, are currently second in Group A, one point behind leaders Serbia, who have played a game more. body check tags ::