The Italian Football Federation (FIGC) said that Frattesi, a goalscorer in Italy's 3-1 win over France on Thursday, has an unspecified "muscular issue" and will return to his club Lazio.
Italy missed the last three World Cups but lead the four-team Group A1, ahead of France thanks to their superior head-to-head record with Les Bleus who also have 10 points from five matches.
A draw against Belgium in Brussels on Sunday would be enough to send Italy to the quarter-finals of the competition.
