Real Madrid forward Gareth Bale has been ruled out of Wales' last two World Cup qualifiers against Georgia and the Republic of Ireland with a calf strain.
The 28-year-old could be out for a month and that would also rule Bale out of the play-offs on 9-14 November.
Wales are second in Group D and if they keep that spot it could be enough to earn them a place in the play-offs.
Bale joined the Wales squad on Monday and, despite sitting out training, it had been hoped he would be fit.
But a scan revealed the severity of the injury and means Bale will not travel to Georgia for Friday's game in Tblisi and will play no part in the Cardiff clash with Republic of Ireland three days later.
Real manager Zinedine Zidane hadplayed down concerns about Bale's fitness, saying he rested him for Sunday's win over Espanyol as a precaution.
Barnsley striker Tom Bradshaw has been called up to the Wales the squad in Bale's place.
Bale's absence is a huge blow to Welsh hopes of qualifying for a first World Cup since 1958.
Wales are second in Group D, trailing leaders Serbia by four points with two matches remaining.
Second place could be enough to earn Chris Coleman's team a place in the play-offs, which will see eight of the nine runners-up in qualifying groups play for four remaining places in Russia 2018.
In order to secure a play-off place, Wales would realistically need at least four points from the games against Georgia and the Republic of Ireland.
Their chances of doing so will be harmed by the injury to Bale, who has scored four goals so far in this campaign.
Wales have failed to win a match without the Real Madrid forward since 2013, drawing three and losing three matches in his absence.
Bale was in Cardiff on Monday to receive his players' player of the year award at the Football Association of Wales' annual ceremony.
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