Full-backs Danny Mills and Chris Powell have played 270 minutes in the last week and both men will not feature against the League 1 side.
This means that French Under-21 captain Yassin Moutaouakil will return at right-back, after impressing early on in the season.
As for the left side of defence, Ben Thatcher is still out with a knee injury so youngster Aswad Thomas could make his Addicks debut.
In the centre of defence, Paddy McCarthy should return and is expected to start alongside Madjid Bougherra.
Between the sticks, it's anyones pick between Nicky Weaver and Darren Randolph, but the latter may get the chance to impress the gaffer.
There will be wholesale changes in the midfield, with Andy Reid and Jose Semedo both being rested after excellent starts to the season.
This gives Matt Holland the chance to return from injury alongside summer signing Therry Racon, who looks to be a star in the making.
Lloyd Sam should remain on the wing, unless Pardew decides to recall Jerome Thomas after his warning. One thing for sure is that Darren Ambrose will start his first game after the birth of his daughter.
And finally, Svetoslav Todorov and Izale McLeod should be given the chance to show what they can do upfront, after Chris Iwelumo and Luke Varney's impressive performances against Norwich and Leicester.
Possible side for Luton: Randolph, Moutaouakil, McCarthy, Bougherra, A Thomas, Sam, Holland (c), Racon, Ambrose, Todorov, McLeod
Subs: Weaver, Fortune, Thomas, Varney, Iwelumo