London Irish centre Jonathan Joseph and Northampton full-back Ben Foden are amongst nine players who have been returned to their clubs.
England coach Stuart Lancaster will name his line up on Thursday morning, but the men retained will either start or be on the bench.
Owen Farrell started at fly-half in the famous 38-21 win over New Zealand in England's last match, and unless Lancaster moves him into midfield - bringing back Toby Flood at 10 - Twelvetrees is likely to partner Brad Barritt in midfield in the Calcutta Cup showdown at Twickenham.
Notable returnees to the squad include hooker Dylan Hartley, who has recovered from the knee injury which kept him out of the November Internationals, wing David Strettle and Flood, who missed out on the New Zealand game with an injured ligament in his toe.
Lancaster said: "We've had to make some tough calls with a lot of competition for places.
"The players' attitude and application in training has been first rate and we know those going back to their clubs and playing in the LV= Cup will be pushing hard for contention for the Ireland match."
Joining Foden and Joseph back at their clubs this weekend are Mouritz Botha, Lee Dickson, Matt Kvesic, Ugo Monye, Henry Thomas, Billy Vunipola and Thomas Waldrom.
Forwards:Cole, Hartley, Haskell, Launchbury, Lawes, Marler, Morgan, Parling, Robshaw, M Vunipola, Wilson, Wood, T Youngs
Backs: Ashton, Barritt, Brown, Care, Farrell, Flood, Goode, Strettle, Twelvetrees, B Youngs
Source : http://www1.skysports.com/rugby-union/news/12504/8454168/Billy-Twelvetrees-named-in-England-s-23-man-squad-for-Calcutta-Cup