The defender is facing up to 12 weeks out after dislocating his shoulder in the first leg in Macedonia, where it finished 1-1.
Summer-signing Paul Quinn replaced his former Motherwell team-mate in central defence in Skopje and could be set for an extended run in the team. Andrew Considine is another who could plug the gap.
McInnes said: “Paul’s someone who, since he came in the door, has played and trained the way we expected him to. He brings a level of experience to the position and he’s a really good competitor.
“He came here to play and obviously Ash Taylor and Mark Reynolds have been a mainstay when they have been fit and available, but Mark’s disappointment is someone else’s opportunity.”
Niall McGinn grabbed the away goal last week and McInnes feels his side will be a lot sharper this time around.
He said: “It was good to get the first game played and since then the standard in training has been better again. The players that played have felt the benefit of that competitive match.”
Shkendija striker Hristijan Kirovski believes his club can make history at Pittodrie; the Macedonians have never won a European tie but Kirovski insists victory can be theirs on Thursday.
He told the Press and Journal: “Aberdeen are the favourites because they have the away goal and home advantage, but we are heading there in relaxed mood and we have prepared ourselves.
“The first 20 minutes will be the most important but if we can start well we can set the tempo of the game and give ourselves a chance. I think we have a chance and if we get the first goal we can go through.”
Croatian side Rijeka await the winners in the second qualifying round.