Fit-again Ireland duo Caelan Doris and Joey Carbery have been recalled for summer Tests against Japan and the United States, while Andy Farrell's experimental squad includes 11 uncapped players.
The substantial uncapped contingent is comprised of Munster pair Gavin Coombes and Fineen Wycherley, Leinster trio Harry Byrne, Peter Dooley and Ross Molony, Ulster players Robert Baloucoune, Tom O'Toole and Nick Timoney, plus Connacht threesome Caolin Blade, Tom Daly and Paul Boyle.
Ireland take on Japan on Saturday, July 3 in Dublin before hosting the United States a week later.
A limited number of supporters will be in attendance at the Aviva Stadium for the fixtures for the first time since the 24-14 Guinness Six Nations victory over Wales in February 2020.
Leinster back-row Doris was tipped to star at this year's Six Nations but missed the entire championship due to concussion symptoms.
Munster fly-half Carbery has not played at Test level since the 2019 World Cup due to a persistent ankle problem.
Sexton and fellow former Lions Cian Healy and Keith Earls have been given a break as Farrell seeks to give experience to other players.
The omission of the 35-year-old skipper, who has 99 Ireland caps, will allow Carbery to compete with Ulster's Billy Burns and Leinster's Harry Byrne for the number 10 jersey.
Among the potential Test debutants, versatile number eight Coombes has been selected following an outstanding season for Munster in which he scored 15 tries in 22 games, including four against Zebre on Friday.
Head coach Farrell has a host of key men unavailable due to their involvement in the upcoming Lions tour of South Africa.
Forwards Tadhg Beirne, Tadhg Furlong, Jack Conan and Iain Henderson have been called up by Warren Gatland, along with backs Conor Murray, Bundee Aki and Robbie Henshaw.
Prop Andrew Porter was also selected for Lions duty before his summer was ruined by a toe injury.
Hooker Ronan Kelleher is currently training with Gatland's men but is not part of the Lions tour squad and has been selected by Farrell.
In addition to the raft of absences, CJ Stander has retired since the Six Nations, while fellow South Africa-born forward Quinn Roux is no longer eligible for his adopted nation after ending his time at Connacht.
Farrell, whose squad will assemble on June 22, said in a statement: "I know the players will come in eager to make the most of this opportunity to pull on the green jersey and play in front of supporters at the Aviva Stadium for the first time in 18 months.
"Johnny, Cian and Keith will not be involved in this window as we grow the experience of other players.
"It will be a great opportunity to see if this group can perform at this level."
Backs: W Addison (Ulster), R Baloucoune (Ulster), C Blade (Connacht), B Burns (Ulster), H Byrne (Leinster), J Carbery (Munster), C Casey (Munster), A Conway (Munster), S Daly (Munster), T Daly (Connacht), C Farrell (Munster), J Gibson-Park (Leinster), H Keenan (Leinster), J Larmour (Leinster), S McCloskey (Ulster), G Ringrose (Leinster), J Stockdale (Ulster).
Forwards: R Baird (Leinster), F Bealham (Connacht), P Boyle (Connacht), E Byrne (Leinster), G Coombes (Munster), U Dillane (Connacht), P Dooley (Leinster), C Doris (Leinster), D Heffernan (Connacht), R Herring (Ulster), R Kelleher (Leinster), D Kilcoyne (Munster), R Molony (Leinster), P O'Mahony (Munster), T O'Toole (Ulster), J Ryan (Leinster, capt), J Ryan (Munster), N Timoney (Ulster), J Van Der Flier (Leinster), F Wycherley (Munster).