Hearts striker Steven Naismith, a surprising inclusion in the Scotland squad for the international break due to a hamstring complaint having restricted him to just three appearances for Hearts this season, has been ruled out of the Belgium clash.
The 32-year-old was omitted from the matchday squad against Russia and won't be risked against Roberto Martinez's side.
Rangers midfielder Ryan Jack has also left the squad after a knee complaint.
Manager Steve Clarke, who is expected to make up to five changes against the top-ranked team in the world, insisted there was little point in naming the former Norwich striker among his substitutes.
“Naismith is close,” Clarke said.
“I could push him, but no, I wouldn’t do that to him. I could sit him on the bench but I don’t think I would use him from the bench as I don’t think it’s worth the risk.
“[Jack] had a little bit of swelling on his knee on Friday and was prepared to sit on the bench, but on Saturday morning there was a little bit more swelling and Rangers decided to go safety first. He has gone back.
"With such a short space between the games you are always going to get one or two little knocks - one or two boys a little bit tired,” he added.
“I think I made five changes in Brussels [in June].
"Two of them were enforced because Andy (Robertson) was out and Ryan Fraser didn’t think he could play 90 minutes. Maybe a similar situation tomorrow, maybe a little bit less.”
Clarke is rumoured to be considering handing starting berths to Celtic's Ryan Christie, Norwich City's Kenny McLean, Matt Phillips of West Brom and West ham midfielder Robert Snodgrass.