Goalkeepers Darren Ward (hamstring) of Sunderland and Lewis Price (thigh) of Ipswich are also out injured.
Wales had already called up keeper Danny Coyne and Andrew Crofts but will make no more additions to the squad.
Burnley's Coyne and veteran Paul Jones are now the only goalkeepers in the squad, with Ward and Price out.
Price, 22, played in Saturday's 2-0 defeat at Crystal Palace and Wales were assured he was fit to drive to Cardiff to link up with the rest of John Toshack's squad.
But on arrival at the Vale of Glamorgan Hotel, it was soon clear after a medical examination that Price had a thigh strain and was immediately sent back to Portman Road.
Crofts, the adaptable Gillingham midfielder, gives a further option that will be needed after Fletcher's and Ledley's withdrawal.
Ledley limped off against Barnsley on Friday night after taking a bad knock to his knee.
Wigan striker David Cotterill had damaged ankle ligaments in a reserve team match but has travelled to Windsor Park.
The withdrawal of striker Davies increases the chances of Wycombe Wanderers front man Jermaine Easter winning his first Wales cap.
Easter, 24, has impressed by scoring 21 goals in 35 games this season, including another in Wycombe's 2-0 win at Wrexham on Saturday.
That helped him win a call-up to a Wales squad for the first time last week when manager John Toshack announced his 24-man selection.
Jermaine Easter has caught the eye in Wycombe's Carling Cup run
Easter is joined by Wrexham defender Ryan Valentine as the only non-capped players in the squad.
With James Collins and Danny Gabbidon injured, Sunderland's Danny Collins is set to play for the first time since November 2005.
Collins fell out of favour after criticising boss John Toshack for leaving him on the bench in the goalless home draw with Paraguay in March last year.
He then ruled himself out of the end of season matches and admitted in November that he feared his Wales career may be over.
Wrexham centre-back Steve Evans retains his place in the squad after making his debut in November's 4-0 friendly win over Lichtenstein.
Robert Earnshaw is another notable absentee after the Norwich striker was ruled out for the rest of the season with a serious groin injury.
Toshack is also again without Aston Villa full-back Mark Delaney, who has just returned from the United States after a career-saving knee operation and will not play again this season.
Wales squad to face Northern Ireland at Windsor Park, Belfast on Tuesday, 6 February:
Danny Coyne (Burnley), Paul Jones (QPR), Gareth Bale (Southampton), Danny Collins (Sunderland), Richard Duffy (Portsmouth, on loan at Swansea City), Steve Evans (Wrexham), Craig Morgan (Peterborough United), Lewin Nyatanga (Derby County), Sam Ricketts (Hull City), Ryan Valentine (Wrexham), Andrew Crofts (Gillingham), Simon Davies (Fulham), Jason Koumas (WBA), Carl Robinson (Toronto FC), David Vaughan (Crewe Alexandra), Craig Bellamy (Liverpool), David Cotterill (Wigan Athletic), Jermaine Easter (Wycombe Wanderers), Ryan Giggs (Manchester United), Chris Llewellyn (Wrexham), Paul Parry (Cardiff City).
Wales Under-21 squad to play Northern Ireland at the Oval, Belfast on 6 February:
Wayne Hennessey (Wolves), Owain Fôn Williams (Crewe), Mark Bradley (Walsall), Kyle Critchell (Chesterfield), Chris Gunter (Cardiff), Joe Jacobson (Cardiff), Mike Williams (Wrexham), Darcy Blake (Cardiff), Mathew Collins (Fulham), Rob Davies (WBA), David Edwards (Shrewsbury), Dean Grubb (Bristol City), Lloyd James (Southampton), Rhys Williams (Middlesbrough), Owain Warlow (Lincoln), Chedwyn Evans (Man City), Chris Jones (Swansea), Sam Vokes (Bournemouth).
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