England have rested George Ford, Jonny May and Ben Youngs for July's Test matches against the USA and Canada.
Head coach Eddie Jones has opted for youth, naming 21 uncapped players in his preliminary 34-man squad.
The 12 England players involved with the British and Irish Lions' tour of South Africa are unavailable.
Players at Premiership semi-finalists Bristol, Exeter, Sale and Harlequins, plus Championship finalists Saracens, are also absent.
Jones, who will update the squad twice before the matches take place, said: "We'll include players from the other clubs where appropriate, when they become available.
"We've also given some of our senior players the chance to get some important rest and recovery time after back-to-back seasons - and with no proper pre-season."
Flanker Mark Wilson is missing despite being involved in England's most recent outing, a 32-18 defeat by Ireland at the end of the Six Nations, with Leicester prop Ellis Genge the most experienced player in the squad with 28 caps.
Among the uncapped players are Bath duo Tom de Glanville and Max Ojomoh, sons of former England pair Phil de Glanville, who was also captain, and Steve Ojomoh.
Flanker Sam Underhill, who has not played for England this year because of injury, returns to the squad and there is also a place for Jacob Umaga, the nephew of New Zealand rugby legend Tana Umaga.
England face the USA at Twickenham on 4 July before hosting Canada six days later after the original plan to tour North America was abandoned because of the coronavirus pandemic.
"For this group it's a chance to come into the England environment and really show what they can do. We expect them to be enthusiastic, full of energy and we want them to know there is no limit to their horizon," said Jones.
"There is a lot of talent in this squad but the challenge for them is to turn talent into performance. They have the opportunity to take on the world."
Backs: Bassett, Cokanasiga, De Glanville, Dingwall, Hassell-Collins, Kelly, Lawrence, Mitchell, Ojomoh, Parton, Radwan, Robson, Spencer, Steward, Umaga
Forwards: Blamire, Chick, Davison, Ewels, Genge, Heyes, P Hill, T Hill, Ludlam, Ludlow, Martin, Munga, Obano, Reid, Robinson, Singleton, Underhill, Wells, T Willis