The Irish centre-half has missed the last two matches after damaging the shoulder he had surgery on back in January.
McCarthy will eventually require another operation but has this week been given the all-clear to keep playing as the problem will not get any worse.
But boss Neil Warnock will not risk him on Saturday so Jose Fonte and Claude Davis will continue at the back.
Up front, Freddie Sears is pushing to start after impressing as a half-time substitute at QPR on Tuesday on his return from a groin injury.
Calvin Andrew (knee) is still out while Warnock has allowed young left-back Lee Hills and back-up goalkeeper Darryl Flahavan to join Oldham on loan.
Loan signing Isaiah Osbourne could make his Middlesbrough debut at Palace.
The 21-year-old Aston Villa midfielder trained with his new team-mates for the first time on Thursday and should be involved as manager Gordon Strachan looks for his first victory at the helm.
Striker Marcus Bent, who made his debut as a substitute in the 1-0 home defeat by Plymouth last weekend after sealing his own loan move from Birmingham, will also hope for a place in the starting line-up.
Andrew Taylor, who played in the reserves in midweek along with Chris Riggott, is closing in on a return from ankle ligament damage, although the latter is still some way away from first-team contention after ankle surgery.
Skipper Emanuel Pogatetz will be out for around six weeks with a fractured cheekbone while Jeremie Aliadiere (ankle surgery), Seb Hines (knee), Caleb Folan (hamstring) and Matthew Bates (cruciate ligament) remain on the sidelines.
Sporting Life