Wales full-back Liam Williams has been ruled out of Sunday's World Cup semi-final against South Africa after suffering an ankle injury in training.
Scarlets full-back Leigh Halfpenny is in line to replace fellow British and Irish Lion Williams in Yokohama.
Williams is also unlikely to recover for the following week, whether Wales reach the final or play in the third-place play-off.
Wales will announce their team at 03:30 BST on Friday.
Williams, 28, has enjoyed a stunning 2019 having won the European Champions Cup and English Premiership with Saracens and was hoping for an historic hat-trick.
He has won 62 caps for Wales and three for the Lions, and has been first choice in the 15 shirt in Japan apart from the much-changed side that played Uruguay.
Wales also have injury concerns over centre Jonathan Davies, who suffered a knee injury in the win against Fiji and missed the victories over Uruguay and France.
Wales' other first-choice centre Hadleigh Parkes has started all five World Cup matches, despite breaking a bone in his hand in the opening match against Georgia and picking up a shoulder problem against Uruguay.
Wales have already lost Cardiff Blues back-rower Josh Navidi after he damaged a hamstring in Sunday's 20-19 quarter-final win against France.
Navidi was replaced in Wales' 31-man squad this week by Blues wing Owen Lane, with coach Warren Gatland wanting more backline cover.
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All pictures via Huw Evans images