Centre Jonathan Davies has been ruled out of Wales' Six Nations clash with France on Friday after failing to recover from a pectoral injury.
Wales say one of his potential replacements, Ashley Beck of Ospreys, has also been ruled out.
With Scott Williams also absent because of injury, Northampton wing George North could move to centre.
But Perpignan lock Luke Charteris does return after a hamstring injury to boost Warren Gatland's forward options.
British and Irish Lions centre Davies tore a muscle in his chest during Wales' autumn Test against South Africa in November.
The 25-year-old Davies, who will join Clermont Auvergne on a two-year contract next summer, made his comeback for the Scarlets against London Irish in the LV= Cup on 1 February.
He returned to the Wales squad, but was not among the players released back to the regions for the weekend's Pro12 matches.
Beck had been called in to train with Wales amid the midfield injuries.
Seven-times-capped Beck, 23 played for Ospreys in their 75-7 Pro12 win over Treviso on Sunday.
But he pulled out of Wales contention after being dogged by hip problems over the last 12 months.
Wales forwards coach Robin McBryde said: "He [Beck] feels he's not quite ready for the step up into international intensity - he wouldn't be doing himself any justice... he's been pretty honest with himself."
Former Wales scrum-half and captain Robert Jones had already backed North to switch to centre with Scarlets' Liam Williams coming into the back-three.
Versatile Perpignan back James Hook is also a midfield option.
Newport Gwent Dragons captain Andrew Coombs took over from his former regional team-mate against Ireland and could make way when Gatland names his team on Wednesday.
Wales captain Sam Warburton and Gethin Jenkins survived their contributions as Cardiff Blues lost to Glasgow in the Pro12 on Saturday. Jenkins' Wales understudy, Paul James, was also in action, playing the full 80 minutes in Bath's 27-23 Aviva Premiership win at Exeter.
In France, scrum-half Mike Phillips was a Racing Metro replacement against Bayonne in the French Top 14, while Hook, an unused replacement against Ireland, scored 14 points with the boot from full-back in Perpignan's 50-19 defeat at Montpellier.
On Sunday, Phillips' Ospreys challenger Rhys Webb and half-back partner Dan Biggar played 47 minutes of their big win. Wales squad prop Ryan Bevington and lock James King also played their parts at Liberty Stadium.
And number eight Dan Baker, a replacement against Treviso, was also involved after last week being called up to train with the Wales squad alongside Beck.