This will be Picamoles’ first start for Les Bleus since their 23-23 draw with Japan in Naterre last November.
Teddy Thomas (wing) and Yoann Maestri (lock) are the only survivors from that encounter which was the last of a three-Test series which the All Blacks won 3-0.
Picamoles is joined in the back-row by flankers Arthur Iturria and Wenceslas Lauret while Sebastien Vahaamahina packs down next to Maestri in the second-row. Toulon hooker Guilhem Guirado will captain the side and Cedate Gomes Sa and Jefferson Poirot are the two props.
In the backline, Clermont fly-half Camille Lopez is over his injury worries and will wear the number 10 jersey while Baptiste Serin will start at scrum-half and Geoffrey Doumayrou and Mathieu Bastareaud form the centre paring.
Maxime Medard lines up at full-back while Thomas is joined out wide by Damian Penaud, who makes his first appearance for France on the wing after playing as a centre in his five previous Tests.
France: 15 Maxime Medard, 14 Teddy Thomas, 13 Mathieu Bastareaud, 12 Geoffrey Doumayrou, 11 Damian Penaud, 10 Camille Lopez, 9 Baptiste Serin, 8 Louis Picamoles, 7 Arthur Iturria, 6 Wenceslas Lauret, 5 Yoann Maestri, 4 Sebastien Vahaamahina, 3 Cedate Gomes Sa, 2 Guilhem Guirado, 1 Jefferson Poirot
Replacements: 16 Camille Chat, 17 Dany Priso, 18 Rabah Slimani, 19 Paul Gabrillagues, 20 Mathieu Babillot, 21 Antoine Dupont, 22 Anthony Belleau, 23 Gael Fickou
Date: Saturday, November 10
Venue: Stade de France
Kick-off: 21:05 local (20:05 GMT)
Referee: Nigel Owens (Wales)
Assistant referees: Matthew Carley (England), Tom Foley (England)
TMO: Rowan Kitt (England)