Saints centre Francis will not feature for England against Australia
Piers Francis will play no part for England in Saturday's game against Australia (kick-off 3pm).
But Courtney Lawes has been handed a start in the final autumn international fixture, while Dylan Hartley is among the replacements.
When he comes on, co-captain Hartley will break the record for most appearances by an England player at Twickenham.
Hartley is currently locked on 55, alongside Jason Leonard, but he will surpass Leonard's total this weekend.
Francis has been training with England this week and he was retained on Tuesday night but he will not feature against Australia.
Despite that, there is no guarantee he will play for Saints at Sale Sharks on Saturday afternoon.
Saints will name their team for the Gallagher Premiership game at midday on Friday.
“We’ve picked our best 23 for the Australia game," said England boss Eddie Jones.
"We know they have a unique style of attack so our ability to defend that is going to be important.
"We are continually working on our strengths which is our set piece and our defence and they are areas that are progressing nicely.
“I’m really happy with the direction we’re going in terms of the way we play the game. We are developing a unique style of rugby, which is English and the players are proud to play that way.
“The second part is the leadership of the team through the co-captaincy of Dylan Hartley and Owen Farrell has been outstanding.
"We have seen growth in the togetherness of the team and I think we’ve seen that in the spirit in which they’ve played.
“Australia, we know are a traditional rival and we enjoy the occasion of playing them at Twickenham. The spirit of the fans has been outstanding.
"I think the atmosphere during these Quilter Internationals has been the best atmosphere I’ve certainly experienced and we encourage the fans to be at their robust best at the weekend.”
Meanwhile, Saints fly-half Dan Biggar will be on the Wales bench for their clash with South Africa in Cardiff on Saturday.
England matchday squad to face Australia
15 Elliot Daly (Wasps, 24 caps)
14 Joe Cokanasiga (Bath Rugby, 1 cap)
13 Henry Slade (Exeter Chiefs, 16 caps)
12 Ben Te’o (Worcester Warriors, 15 caps)
11 Jonny May (Leicester Tigers, 39 caps)
10 Owen Farrell (Saracens, 64 caps) co-captain
9 Ben Youngs (Leicester Tigers, 79 caps)
1 Ben Moon (Exeter Chiefs, 3 caps)
2 Jamie George (Saracens, 31 caps)
3 Kyle Sinckler (Harlequins, 16 caps)
4 Maro Itoje (Saracens, 25 caps)
5 Courtney Lawes (Saints, 67 caps)
6 Brad Shields (Wasps, 4 caps)
7 Sam Underhill (Bath Rugby, 8 caps)
8 Mark Wilson (Newcastle Falcons, 7 caps)
16 Dylan Hartley (Saints, 96 caps) co-captain
17 Alec Hepburn (Exeter Chiefs, 5 caps)
18 Harry Williams (Exeter Chiefs, 14 caps)
19 Charlie Ewels (Bath Rugby, 9 caps)
20 Nathan Hughes (Wasps, 17 caps)
21 Richard Wigglesworth (Saracens, 32 caps)
22 George Ford (Leicester Tigers, 50 caps)
23 Manu Tuilagi (Leicester Tigers, 26 caps)