Flintoff may be their preferred choice as captain for the defence of the Ashes in Australia later this year, with Michael Vaughan ruled out after knee surgery, but a recurrence of the 28-year-old Lancashire hero's longstanding left ankle problem means his run of 35 successive England Tests is about to end.
In that time Flintoff has had a major impact on England's fortunes, scoring 2,011 Test runs at an average of 38.67 and taking 136 wickets at 26.26 apiece.
"It doesn't take Einstein to work out that in replacing a world-class all-rounder you have to weaken one department or the other," said England's chairman of selectors, David Graveney, earlier this week.
England coach Duncan Fletcher has generally tended to favour a five-man attack, but England's bowling options have been hampered by injuries to Simon Jones (knee), James Anderson (back) and Ashley Giles (hip) as well as Flintoff.
That makes it more likely England will opt for the additional reassurance of an extra batsman with Ian Bell, who made an elegant 74 for England A against Pakistan in the tourists' ongoing warm-up match at Canterbury, likely to come in.
Bell and all-rounder Paul Collingwood could then support a four-man attack with 'fill-in' overs of medium pace.
And were England, who will be captained at Lord's by opener Andrew Strauss, to head to the second Test at Flintoff's Old Trafford home ground later this month, where their talisman is expected to return, with the four-match series still level, Fletcher would probably regard that as an acceptable outcome.
But Collingwood insists there was no place for negative thinking in Flintoff's absence and he said: "We have to believe we can beat Pakistan without him playing at all, so we should regard it as a bonus to get him back."
England's batting order has had a long tail of late with wicket-keeper Geraint Jones, who ousted superior gloveman Chris Read from the side two years ago on account of his better run-getting, enduring a lean time all-round.
Read though showed how his batting had developed in recent seasons by scoring an unbeaten 120 to take England A to 530 for nine on a rain-affected second day of four against Pakistan at Canterbury here Friday.
Fletcher has so far appeared immovable in his support of Jones but Read, for his part, was certainly determined to maintain the pressure on his rival after scoring his third first-class hundred of the season.
"My batting was mooted as the only reason I was axed," said Read, who averages 15 in his 11 Test appearances.
"I could appreciate that lack of runs led to it and in the past two-and-a-bit years I have done a lot of work to get my batting up to scratch," the 27-year-old added.
Read's England career came to a shuddering halt in 2004 despite starring with the gloves in what was the team's first Test series triumph in the Caribbean for 36 years.
"I was devastated to be dropped. Even though I hadn't scored the runs I felt that, while the team were winning and I was performing behind the pegs, the runs would come but that obviously wasn't good at enough at the time," he explained.
"It is frustrating to be on the outside but I also know I have had two chances - one when I was probably a little bit too young and one where I didn't grasp it when I would have loved to have done - so I am hoping to put enough pressure back on the selectors that I get a third chance."
Meanwhile off-spinner Jamie Dalrymple, one of England's few successes during the one-day mauling by Sri Lanka where he impressed with both bat and ball, could be called into a 13-man squad.
One consolation for England is the return to Test action of spearhead fast bowler Stephen Harmison, who has overcome a shin injury, and is set to take the new ball alongside Matthew Hoggard.
Collingwood (thigh and ribs) and batsman Kevin Pietersen (knee) are also expected to be fully fit.