McCann told The Star earlier this week that Ben Whiteman was a doubt for the trip to Kenilworth Road after picking up an ankle injury in last Friday’s 0-0 draw with Barnsley.
Rovers spent the first part of this week relaxing at Champneys Health Spa in a bid to reinvigorate minds and bodies for the run-in.
But McCann told the local media on Thursday he will be forced to make two changes against a Luton side unbeaten in 25 league games.
“We’ll be missing two big players, which is not ideal at this stage of the season,” said McCann.
“But it’s the reason we’ve got a squad.
“It’s an opportunity for two others.
“There’ll be two changes from the last game. That’s the crux of it.
“We’ve got some very good players here who haven’t really had the game time that they would like.
“Now is an opportunity for them.”
Doncaster are one of only four teams to have beaten the Hatters in League One this season following their 2-1 triumph at the Keepmoat Stadium in September.
Should sixth-placed Rovers complete a double this weekend it would give their play-off quest a significant shot in the arm following six league games without a win.
“They’re the best team in the league,” said McCann.
“No one will give us a chance going there.
“But good runs always have to come to an end at some point.
“We’re concentrating on us and not Luton.
“We’re in confident mood,” he added.
“The boys realise we could’ve won the last two.
“We were excellent defensively and in terms of how we dealt with the conditions and the pitch at Blackpool.
“And for 45 minutes we were outstanding against Barnsley. We should’ve won that game but we didn’t.
“The message to the group is to start turning these draws into wins now and that’ll see us over the line.”