McCarthy serves a one-match ban after he was sent off during the Carling Cup semi-final penalty shoot-out defeat at Cardiff last week.
Hull loanee Paul McShane, who six years ago scored a famous winner for Brighton at Selhurst Park, is likely to step in at centre-half against his old club.
Palace fans will be anxious to see whether defender Nathaniel Clyne and winger Wilfried Zaha are involved with both players linked with moves to the Premier League ahead of the 11pm deadline.
Left-back Dean Moxey is fit after a spell out with a knee injury and right-back Mustapha Dumbuya returns after he was cup-tied last week.
Sam Vokes could be thrown in at the deep end for his Brighton debut. The Wales striker has signed on loan from Wolves until the end of the season and will be in the squad.
Midfielder Matt Sparrow looks set to miss out after suffering an ankle injury during Saturday's FA Cup win over Newcastle, so Alan Navarro could start.
Winger Kazenga LuaLua is back in training after a hamstring injury and should travel but defender Marcos Painter is still struggling with his hamstring problem.
Centre-half Tommy Elphick (Achilles) and midfielder Gary Dicker (broken leg) remain long-term absentees for the Seagulls, who are desperate for revenge after Palace inflicted their first league defeat at their new Amex Stadium back in September.
Crystal Palace V Brighton - view commentary, squad, and statictics of the game live.