Belgium host Greece in Brussels on Saturday as Roberto Martinez's men look to continue their perfect start to their Group H campaign.
The Red Devils are already without Eden Hazard (calf) and they will also have to make a late decision on Manchester City playmaker De Bruyne, who sustained a groin problem in training on Thursday.
"Kevin is a vital player and we will wait until the very last second to decide," said Martinez.
City will be anxiously following developments, with a key Premier League match away to Arsenal following the international break on April 2.
Belgium have won four straight games in qualifying, while closest challengers Greece are just two points behind going into the match.
After the Greece game, Belgium, who are ranked fifth in the world, play an away friendly against Russia next Tuesday.