Brendon McCullum is not risking James Anderson or Ollie Robinson, who have been struggling with minor groin and ankle injuries respectively, while Mark Wood is also being given time off.
With Chris Woakes also missing, England will be under strength although they still have plenty of experience with Ben Stokes, Stuart Broad and Jonny Bairstow all involved.
And they will be eager of continuing the momentum built over the past 12 months as they ramp up preparations for their summer showdown with Australia.
“It would be a completely different-looking team if this was Australia tomorrow,” said Stokes on Wednesday.
“We have had to look at risk versus reward and I didn’t feel this game was worth taking the risk particularly with Jimmy and Robbo.
“They’ve come off the back of little niggles. It is the sensible thing to do not to put those guys at risk.”
Fast bowler Josh Tongue stands to benefit from England’s high-profile list of absentees as he will make his Test debut after a surprise call-up this week.
“It’s an amazing feeling,” Tongue said. “I’m speechless really, even from when I got the first call up to be in the squad. Now being in the actual team, it’s just a dream come true really.
“I’ve never played at Lord’s before for Worcester so it’s my first time being here and experiencing the ground. It’s an amazing feeling, and to make my Test debut as well.
“I’ve come to watch Test matches with my family, my Dad, but first time playing here.”
How to watch England vs Ireland Test
Dates: Thursday 1 June – Saturday 4 June
Time: 11am BST
TV: Sky Sports Cricket and Main Event, coverage begins at 10am
Stream: NOW. You can purchase a day pass for £11.98 or a monthly pass for £34.99
Ireland are yet to win a game since gaining Test status in 2017 but will be eager to make things awkward for England as they continue to adjust to the format.
They gave England a scare back in 2019, bowling them out for 85 before lunch in the first Test before eventually losing by 143 runs as their opponents fought back.
Ireland coach Gary Wilson will be without his star bowler Josh Little, who is being rested ahead of the World Cup qualifying tournament in Zimbabwe in June, but is adamant his side can cause an upset.
“There’s been a lot of chat about the way they’re playing now and their so-called Bazball,” he said. “But if we try and play our game and back our skill level, which the lads have shown especially individually over the last 18 months, I think we definitely have a chance to get a favourable result here.”