Without the insurance of the combative De Rossi, the Italy coach has brought Claudio Marchisio and Angelo Palombo into midfield.
"I thought seriously about playing two strikers with Antonio Cassano behind. Then without De Rossi I had to alter my idea. He doesn't have a clone," Prandelli told a news conference on Monday, saying other changes followed watching DVDs of Serbia.
Striker Giampaolo Pazzini will replace Marco Borriello, who lacked conviction in front of goal in Friday's 0-0 draw in Northern Ireland which kept Italy top of Group C.
Stefano Mauri, who impressed in his all-action display on Friday in his first Italy appearance since 2007, is likely to move into Pepe's role out wide with forward Cassano teaming up with Pazzini on their Sampdoria home ground.
Vladimir Petrovic, whose side were embarrassed 3-1 at home by Estonia on Friday in his first game in charge, said: "I can't tell you much about the formation, it's a fundamental game. I can say that Neven Subotic will be on the field, he is a valid alternative to the suspended Nemanja Vidic."
"A draw would be a good result," the coach added. "It will be a difficult game for both sides, both of us played badly in the last match."
