The match at the Stadio Olimpico in Rome on Saturday launches the 2021 competition with France heavily tipped to usurp England as champions.
The billing comes after a second string France team pushed England close in the Autumn Nations Cup final at Twickenham in December.
Following an agreement between the French rugby federation and the the country's top flight clubs, Galthié had to make 13 changes to his team for the last two games of the Autumn Nations Cup.
England won 22-19 after extra-time.
Bonus
"The changes we had to make in the autumn allowed us to give some uncapped players a little bit of experience with the squad and a taste of international test rugby,” said Galthié.
“It gave us the opportunity to develop more depth to the team. That will help us deal with injuries during the Six Nations a little bit better."
France will be without fly-half Romain Ntamack for the match. He is recovering from a broken jaw.
The 21-year old was one of the stars of the 2020 Six Nations. He scored 57 points in five matches and formed a flamboyant partnership with scrum-half Antoine Dupont who was ultimately named player of the 2020 tournament - the first Frenchman to win the accolade since its inception in 2004.
France are also without winger Virimi Vakatawa and full-back Thomas Ramos.
“It’s true that Vakatawa has the capacity to beat his marker and great power but we have other players with different qualities and his absence will not change our way of playing," said Galthié somewhat disingenuously.
Veteran Brice Dulin returns to the fold for Ramos and Matthieu Jalbert, who featured in the loss to England, will step in for Ntamack.
Discipline
Galthié has opted to crack down on team discipline on the pitch by drafting in the former international referee Jérome Garces to help them navigate the rule book. Garces, 47, retired from officiating after taking charge of the 2019 World Cup final.
"I do not particularly feel like we're favourites,” added Galthié.
“That’s something attributed to us by the media. We're preparing for and focusing on our first game against Italy. That’s our state of mind. If we are going to dethrone England, we will need to be very good, and that's what we're aiming for.”
Italy, who have finished bottom of the table on 15 occasions since the tournament was expanded in 2000, are not expected to pose too many problems for Galthié’s men.
England begin the defence of their crown at Twickenham against Scotland on Saturday and the first round of games concludes on Sunday with Wales hosting Ireland in Cardiff.
"We hope to do better than last year,” added Galthié.
