The potential debutants are Edinburgh trio Blair Kinghorn (full-back), scrum-half Nathan Fowles and prop Murray McCallum, plus Glasgow Warriors prop D’arcy Rae.
John Barclay continues as captain as Greig Laidlaw returns to the squad after recovering from an ankle injury.
Worcester back-rower David Denton returns to the squad, as does Edinburgh centre Mark Bennett, who has recently returned after a long-term knee injury.
There is no place for hooker Fraser Brown, who has suffered a number of head injuries this season, but there is a return for Scott Lawson of Newcastle Falcons.
Townsend said: “With the announcement of this 40-man squad, we are now entering the key stages of our preparation for this year’s NatWest Six Nations Championship.
“It’s a bigger squad than we originally planned – which is largely down to the competition for places – with a number of players having performed well in the Autumn Tests and a few others putting their hands up for selection in recent weeks.
“We welcome Blair Kinghorn into our group for the first time, who has been in excellent form with Edinburgh this season, and also three of our most experienced players in Richie Gray, Greig Laidlaw and Scott Lawson.
“We are looking forward to working with them and the rest of the squad to ensure that we build on the momentum the players generated in 2017.”
In addition to the squad, three players have been invited to train with the group: Luke Crosbie (Edinburgh), Darcy Graham (Edinburgh) and Adam Hastings (Glasgow Warriors).
The squad comprises 17 Glasgow Warriors players, 11 from Edinburgh, three from Newcastle Falcons including Jon Welsh, two from Saracens, and one each from ASM Clermont Auvergne, Scarlets, London Irish, Leicester Tigers, Worcester Warriors, Sale Sharks and Toulouse.
SCOTLAND SQUAD FOR 2018 NATWEST 6 NATIONS
Mark Bennett (Edinburgh Rugby) – 20 caps
Alex Dunbar (Glasgow Warriors) – 28 caps
Nick Grigg (Glasgow Warriors) – 1 cap
Chris Harris (Newcastle Falcons) – 1 cap
Stuart Hogg (Glasgow Warriors) – 55 caps
Pete Horne (Glasgow Warriors) – 28 caps
Ruaridh Jackson (Glasgow Warriors) – 32 caps
Huw Jones (Glasgow Warriors) – 11 caps
Lee Jones (Glasgow Warriors) – 7 caps
Blair Kinghorn (Edinburgh Rugby) – uncapped
Greig Laidlaw (ASM Clermont Auvergne) – 58 caps
Sean Maitland (Saracens) – 29 caps
Byron McGuigan (Sale Sharks) – 2 caps
Ali Price (Glasgow Warriors) – 11 caps
Henry Pyrgos (Glasgow Warriors) – 27 caps
Finn Russell (Glasgow Warriors) – 32 caps
Tommy Seymour (Glasgow Warriors) – 39 caps
Duncan Taylor (Saracens) – 21 caps
Nathan Fowles (Edinburgh Rugby) – uncapped
John Barclay CAPTAIN (Scarlets) – 66 caps
Simon Berghan (Edinburgh Rugby) – 5 caps
Jamie Bhatti (Glasgow Warriors) – 3 caps
Magnus Bradbury (Edinburgh Rugby) – 2 caps
David Denton (Worcester Warriors) – 35 caps
Cornell Du Preez (Edinburgh Rugby) – 5 caps
Grant Gilchrist (Edinburgh Rugby) – 18 caps
Jonny Gray (Glasgow Warriors) – 38 caps
Richie Gray (Toulouse) – 64 caps
Luke Hamilton (Leicester Tigers) – 1 cap
Rob Harley (Glasgow Warriors) – 20 caps
Scott Lawson (Newcastle Falcons) – 46 caps
Murray McCallum (Edinburgh Rugby) – uncapped
Stuart McInally (Edinburgh Rugby) – 12 caps
Gordon Reid (London Irish) – 27 caps
D’arcy Rae (Glasgow Warriors) – uncapped
Ben Toolis (Edinburgh Rugby) – 7 caps
George Turner (Glasgow Warriors) – 2 caps
Hamish Watson (Edinburgh Rugby) – 15 caps
Jon Welsh (Newcastle Falcons) – 11 caps
Ryan Wilson (Glasgow Warriors) – 32 caps