The Real Madrid forward missed the 1-1 draw with Atletico Madrid on Sunday with a thigh injury, but came off the bench during a surprise 1-0 defeat to Lille in the Champions League on Wednesday.
Despite recovering from the issue, France head coach Didier Deschamps has not selected the 25-year-old for matches against Israel and Belgium.
“I had an exchange with Kylian.
He has a problem which is not serious.
I am not going to take risks, which is why he is not in the squad,” Deschamps told reporters in Paris.
Mbappe has scored seven goals in 10 appearances since joining Real Madrid in the summer.
Another notable absentee is Antoine Griezmann, who announced his retirement from international football on Monday.
“He had such an impact that we can’t play in the same way,” Deschamps said of losing Griezmann, who retired aged 33 after winning 137 caps.
“I am not necessarily going to change the system, but I am not going to look for an equivalent player.”
Chelsea attacker Christopher Nkunku, who won the last of his 10 caps in June last year, returns to the squad, while midfielder N’Golo Kante misses out.
France will play their away fixture against Israel on Thursday, 10 October in Budapest due to security concerns in the Middle East.
Les Bleus will then face Belgium in Brussels on Monday, 14 October.
France are currently second in Group 2 of League A with three points after two games, while Italy are top with six points.
Goalkeepers: Alphonse Areola (West Ham United), Mike Maignan (AC Milan), Brice Samba (Lens)
Defenders: Jonathan Clauss (Nice), Lucas Digne (Aston Villa), Wesley Fofana (Chelsea), Theo Hernandez (AC Milan), Ibrahima Konate (Liverpool), Jules Kounde (Barcelona), William Saliba (Arsenal), Dayot Upamecano (Bayern Munich)
Midfielders: Eduardo Camavinga (Real Madrid), Youssouf Fofana (AC Milan), Matteo Guendouzi (Lazio), Manu Kone (Roma), Aurelien Tchouameni (Real Madrid), Warren Zaire-Emery (Paris St-Germain)
Forwards: Bradley Barcola, Ousmane Dembele, Randal Kolo Muani (all Paris Saint-Germain), Christopher Nkunku (Chelsea), Michael Olise (Bayern Munich), Marcus Thuram (Inter Milan)
