Arsenal meet Chelsea at Wembley on Saturday looking to salvage silverware from a season that has seen them fail to qualify for the Champions League for the first time in 20 years.
Laurent Koscielny is suspended, Gabriel is out injured and Skhodran Mustafi is a doubt following a concussion – a combination of events manager Arsene Wenger described as "absolutely unbelievable".
Mertesacker is therefore set to start for the first time in over a year in the biggest match of Arsenal's season, leaving former Gunners star Merson far from confident.
"Arsenal are struggling in defence," Merson, who is predicting a 3-1 Chelsea win, told Sky Sports.
"If both teams had brought their A game then Chelsea would still have won, but with Laurent Koscielny and Gabriel out, Shkodran Mustafi potentially out and Per Mertesacker playing at the back I would be shocked if Arsenal got a result.
"With Arsenal's defence, I can't see them coping with Chelsea's attacking flair. We saw Tottenham play very well in the semi-final and they still let in four goals. Tottenham were the better team on that day and still lost.
"Arsenal need to have their best defenders playing to have any chance and they haven't."
On Wenger's options, Merson added: "I think the missing players will mean Arsenal have to go four at the back. If Mustafi plays, they could play him with Mertesacker and Rob Holding as a three. But if he doesn't then you only really have Mertesacker and Holding.
"If you start playing Nacho Monreal as one of the three then he won't be able to cope with Diego Costa.Terry responds to farewell criticism
"They would have to play Mertesacker in the middle because of his lack of pace and then Chelsea would play diagonal balls to Costa who will sit on Monreal and he will win every header and they will go from there. It's a dangerous one for Arsenal if they play three at the back.
"Mertesacker is going to be crucial for Arsenal if he plays; he will have to play very well if Arsenal are to have any chance. If he doesn't play well then Chelsea are going to cut through Arsenal like a knife through butter."
Arsenal beat Chelsea 3-0 at Emirates Stadium in September, but suffered a 3-1 loss in the return fixture.