England will not select any Leicester, Wasps or Bath players involved in next month's European finals for either summer Test against South Africa.
Leicester and Wasps are in the Heineken Cup final on 20 May, just six days before the first Test, with Bath in the European Challenge Cup final on 19 May.
The two clubs supplied nine of the starting line-up for England's most recent Test, including the entire pack.
Coach Brian Ashton will announce his severely depleted squad on Tuesday.
England had already confirmed that players from the three clubs would not be considered for the first Test in Bloemfontein, but Ashton decided he would not call on them for the second Test in Pretoria on 2 June either.
"I've reached the decision based on three principles," said Ashton.
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"Firstly, the players will not have time to prepare and acclimatise for the first Test match.
"Secondly, after their massive efforts spent in reaching the Heineken and European Challenge Cup finals, the players have the chance to recharge their batteries before the World Cup warm-up camps.
"Finally, I also feel very strongly that the players I will select for the touring squad must be trusted and respected to fulfil the two fixtures against South Africa."
Wins for Leicester, Wasps and Bath provided the worst possible outcome for Ashton, whose life has not been made any easier by injuries to Tim Payne, Olly Morgan and Mike Tindall or the six-month suspension handed to Dylan Hartley.
England's resources will be stretched to breaking point in the front row, with Phil Vickery, Julian White, George Chuter, Lee Mears, Matt Stevens and Perpignan's Perry Freshwater all set to miss out because of their club commitments, while Sale's Andrew Sheridan is recovering from a knee injury.
Ashton could turn to promising Gloucester loose-head Nick Wood, or veterans such as Saracens' Kevin Yates and Bristol's Darren Crompton at prop alongside Sale's Stuart Turner, who played six minutes during the Six Nations.
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Saracens' Matt Cairns and Sale's Andy Titterrell could travel as hookers, with Bristol's Mark Regan also set for a recall.
Gloucester's Alex Brown, Sale's Chris Jones and Dean Schofield, Bristol's Roy Winters and London Irish's Nick Kennedy are all in contention for selection in the second row.
And the back row could feature a recall for Saracens' Richard Hill alongside the likes of Sale's Magnus Lund, Harlequins' Nick Easter and Gloucester duo Andy Hazell and James Forrester.
Ashton is better off behind the scrum, with the Newcastle contingent of Jonny Wilkinson, Toby Flood and Mathew Tait all available - injury permitting - along with Mike Catt, Jason Robinson, Andy Farrell, Shaun Perry, Mark Cueto and David Strettle.
England also need to select a "second-string" Saxons squad for the Churchill Cup against Scotland A, Ireland A, the United States, Canada and New Zealand Maori.
The tour is part of England's preparations for the World Cup defence in France which begins on 7 September.
England have three other warm-up matches before the tournament gets under way - against Wales on 4 August and against France on 11 and 18 August.