The centre-back missed Arsenal's Premier League defeat at Manchester United on Sunday due to illness and he will not feature for his country in Milan.
However, Germany coach Joachim Low revealed that the former Werder Bremen man could play at Wembley on Tuesday.
"Per Mertesacker will remain in London and will join us when we are there for the game," said Low, who will take charge of his country for the 100th time on Friday.
Bundesliga top two Bayern Munich and Borussia Dortmund lock horns in the first round of club fixtures after the international break, but Low insists that will not be a factor in his selection for the two friendlies.
"I don't think the players are thinking about it yet, I have always tried to consider clubs in my decisions but I do not want anyone to come to me and tell me to rest them on Friday or Tuesday," he added.
"I have told them there are not many games left until the World Cup. If someone thinks they are automatically picked then they are wrong. I demand full speed ahead from everyone. We've got a high level squad and there are no free passes to Brazil."
Strike duo Miroslav Klose and Mario Gomez will not feature in either game due to injury, but Mesut Ozil (virus) has been passed fit.
Bayern playmaker Mario Gotze and Borussia Moenchengladbach striker Max Kruse are set to feature in the absence of Klose and Gomez, and Low believes the friendlies will provide an opportunity for Germany to test the strength of their squad.
"It is part of our job to build up players who can fill gaps," he added.
"Obviously, it is a pity that Mario and Miro are out but I do not see a problem. For me, January is the cut-off date.
"If a player starts the new year normally after completing winter training and then plays through then I am certain he will join us in good form."
