Uncapped duo Ashton Hewitt and Aaron Wainwright were called up to the Wales squad for their June Tests as a Premiership trio were released.
The Dragons pair and Ospreys prop Rhodri Jones were added to the squad for Tests against South Africa (June 2) and Argentina (June 9 and 16).
The trio were called up as replacements for Worcester Warriors' Josh Adams, Exeter Chiefs' Tomas Francis and Bath's Luke Charteris, who would not be released by their Premiership clubs for the South Africa clash – which falls outside the Test window.
"We are really disappointed that Josh, Tomas and Luke have to miss out on the opportunity to tour with Wales and play international rugby this summer," Wales head coach Warren Gatland said.
"It was a great opportunity for them to play for their country, press their claim in an important year and it is a shame supporters will not get to see them in the red of Wales.
"The situation is very clear for players playing in England going forward and heading into a RWC [Rugby World Cup] year.
"With the players unavailable to link up with the squad until the week of our second Test match we have had to replace them in the squad."
Cardiff Blues' Josh Navidi has also been ruled out after suffering a dislocated shoulder in his team's European Challenge Cup final win over Gloucester on Friday.
Forwards: Rob Evans, Alun Wyn Jones, Nicky Smith, Elliot Dee, Ryan Elias, Rhodri Jones, Samson Lee, Dillon Lewis, Adam Beard, Bradley Davies, Seb Davies, Cory Hill (co-captain) James Davies, Ellis Jenkins (co-captain), Ross Moriarty, Aaron Wainwright, Aaron Shingler.
Backs: Aled Davies, Gareth Davies, Tomos Williams, Gareth Anscombe, Rhys Patchell, Hadleigh Parkes, Owen Watkin, Scott Williams, Hallam Amos, Steff Evans, Ashton Hewitt, George North, Tom Prydie.
|Nadal: Victory over Ebden a step forward|
|Proteas rest Steyn and De Kock for opening ODIs|
|Nadal and Federer march on as rising stars prosper|
|Barcelona president Bartomeu convinced Valverde will stay|
|Inter forward Keita suffers thigh injury|
|Nadal races into third round with easy Ebden win|
|Kimmich ´perfect´ for Barcelona, says Xavi|
|Richardson and Nabi inspire Renegades´ rout of Sixers|
|This Liverpool isn´t a team of chokers – Mane|
|Central Coast Mariners 2 Melbourne City 1: Late Simon winner ends 10-match losing streak|
|Bryan backs Murray to return after hip resurfacing surgery|
|Scotland coach Townsend turns to trio of uncapped hookers|
|Spurs´ Aurier arrested on suspicion of assault, released without charge|
|That was a fireworks show - Warriors revel in record-breaking first quarter|
|We are in talks with Chelsea – Salihamidzic reiterates interest in Hudson-Odoi|
|´Proud´ Messi recognises impact of team-mates after reaching 400 LaLiga goals|
|Henry v Vieira: The Arsene Wenger proteges to move into coaching|
|Federer enjoys ´cat and mouse´ win over Evans|
|Wozniacki cruises through in Melbourne|
|Federer maintains perfect Australian Open second-round record|
|Warriors set NBA record, Butler´s 76ers rout Timberwolves|
|´I like the fact we beat them´ - 76ers´ Butler revels in win over Timberwolves|
|Murray says he´ll ´probably´ have operation|
|Australian Open tribute for Andy Murray surprises brother Jamie|
|Warriors score NBA record 51 points in first quarter against Nuggets|
|Panthers owner Tepper doesn´t rule out Newton missing 2019 because of shoulder injury|
|De Ligt will be world´s best centre-back – Koeman|
|Ronaldo a ´perfect machine´, says Gattuso|
|Barcelona? I can´t say anything - Stuani|
|Silva upbeat about Man City title chances|
|Celtics youngsters say Irving´s callout ´came from a good place´|
|NFL playoffs: Patrick Mahomes v Tom Brady|
|NFL playoffs: Jared Goff v Drew Brees|
|Sixers sign Brewer to 10-day contract|
|Lozano and Morgan scoop CONCACAF awards|
|Lakers ´optimistic´ about LeBron injury|
|Giants produce mammoth fourth quarter against Nymburk|
|Austin FC to join MLS in 2021|
|Henry, Vieira look forward to reunion when Monaco host Nice|
|Barcelona reject Neymar phone call reports|
|Wentz is the quarterback ´going forward´, says Eagles coach Pederson|
|Gattuso: Higuain has not asked to leave|
|Drew Brees by the Opta numbers: 10 facts for QB´s milestone birthday|
|Harry Kane injury: England captain´s history of ankle woe|
|Harry Kane injury: Opta numbers suggest Spurs struggles|
|Harry Kane injury: Tottenham´s options in striker´s absence|
|Allegri: Supercoppa clash practice for Champions League knockouts|
|First in clean sheets, second to Schmeichel in titles – Cech´s Premier League career in Opta numbers|
|Warrington sign England star Widdop|
|Gatland confident Wales can win Six Nations|
|Fulham sign Netherlands international Babel|
|Harry Kane injury: Games the Tottenham striker will miss|
|Simeone focused on matches, not transfer dealings|
|Iran v Iraq: Pressure off for Queiroz & Katanec|
|Vietnam v Yemen: Kocian keeps the faith|
|Darren Bravo back in West Indies Test side for first time since 2016|
|Kane out until March with ankle injury|
|South Korea v China: Son arrives for Group C dead rubber|
|Kyrgyzstan v Philippines: Eriksson remains hopeful|
|McGrath to miss Six Nations, Sexton nearing fitness|
|Kohli savours Dhoni ´classic´|
|Ford: People obsess over Farrell fly-half battle|
|EFL asks Leeds to explain ´spygate´ scandal|
|No alarms for Djokovic and Zverev, Raonic masters Kyrgios|
|Australia 3 Syria 2: Rogic breaks hearts with stoppage-time winner|
|Palestine 0 Jordan 0: Socceroos winner keeps hopes alive for Lions of Canaan|
|Halep: The results don´t matter any more|
|Hard work for Halep as Serena and Osaka sail through|
|Napoli director to take legal action over ´false´ quotes about Rog move|
|Alexander-Arnold facing absence of up to four weeks|