The 30-year-old's omission is precautionary as he does not want to aggravate his Achilles injury playing with the Azzurri, who have already qualified for the World Cup in Brazil
The midfielder has played the full 90 minutes in all of Roma’s seven matches this season, including Saturday’s 3-0 win over Inter at San Siro, despite the injury.
The international break will serve as a welcome two-week rest for De Rossi to get fully fit before returning to Serie A action on October 19 against Napoli.
With Italy already assured of their place in the 2014 World Cup, they can afford to give players rest ahead of their final two qualifiers against Denmark and Armenia.
De Rossi has been capped 93 times for the Azzurri, scoring 15 goals.
Cesare Prandelli has a wealth of options to replace the 30-year-old in central midfield, with Paris Saint-Germain’s Thiago Motta and Marco Verratti, or AC Milan’s Andrea Poli all capable of filling the void.