Gayle, who scored in Palace's impressive 3-1 win over Liverpool on their last outing at Selhurst Park, was substituted during the first half of Saturday's 1-1 draw at Swansea City with a back injury.
James McArthur replaced Gayle - bolstering the London side's midfield after a shaky start during which Wilfried Bony opened the scoring - and manager Neil Warnock must ponder whether to stick with that change in shape against a Villa side without a win in their past nine matches.
Another fitness issue for Warnock to contend with comes at centre-back, where Brede Hangeland deputised for Damien Delaney against Swansea after the latter sustained a calf problem in the Liverpool match.
Palace's defence will contend with a Villa attack that was bolstered by Joe Cole last time out - the former England playmaker marking his first Premier League start for the club with a goal in the 1-1 draw at Burnley.
Villa have been woefully shot shy during their barren run and manager Paul Lambert hopes Cole can help to provide greater creativity in the final third as his fitness improves.
Lambert told Villa's official website: "The big plus [against Burnley] was Joe Cole with the way he played - I thought he was outstanding. He was exceptional.
"I thought he was a massive plus and it was a great goal he scored.
"He's getting fitter and fitter with every passing week. He has great enthusiasm for the game of football for a guy who has won everything in the game. His performance was outstanding."
Both teams are locked together on 13 points, two above the relegation zone, with Villa's lack of success in the opposition penalty area leaving them seven worse off than Palace on goal difference.
Cole became only the third player after Andreas Weimann and Gabriel Agbonlahor to score for Vila in the league this term and striker Christian Benteke will hope to add his name to this paltry number as he returns from a three-match suspension.
Lambert remains hindered by a lengthy injury list that includes defensive trio Nathan Baker (knee), Ron Vlaar and Philippe Senderos (both calf) and England midfielder Fabian Delph (shoulder).
Palace triumphed when the teams met at Selhurst Park in April last season, with winger Jason Puncheon scoring the only goal of the game.
‘I don’t think Liverpool would look at Ollie Watkins, a striker isn’t a pressing issue for them – it’s Arsenal who need one’ Former Reds star explains why his old club don’t need an out-and-out forward this summer
‘He’ll still be playing at 40 at a good level because he’s in such good shape and looks after himself so well. He does everything to be a top professional’: Ex-Liverpool coach insists Mohamed Salah has plenty more miles in the tank
