Belgium head coach Marc Wilmots has confirmed the Jan Vertonghen will play no further part in the remainder of their Euro 2016 campaign after he sustained torn ankle ligaments in training and is facing six to eight weeks out.
The Tottenham defender, who has predominantly featured at left-back throughout the tournament in France, sustained the injury during training ahead of Belgium's quarter-final tie against Wales on Friday.
Vertonghen's absence is a blow to Wilmots, who is already without suspended Barcelona defender Thomas Vermaelen.
"I blew the whistle to stop training and he turned his ankle as he brought the ball down," Wilmots told reporters on Thursday.
"He had a scan here and he has torn two or three external ligaments, which mean his Euros are over.
"It's a sporting tragedy for him - I won't say it's a real tragedy. He was completely fit mentally and physically but fate decided that on this particular movement, that he would do 10,000 times his ligaments would tear.
"He was our vice-captain and we've got Thomas Vermaelen, who's banned. But we've got alternatives. We face a tricky fixture but the players have been with us for four years.
"We have options there. We're thinking forward, to the future. We've got 19 players fit and ready to play and we have to try to get into the last four."
Asked about a timescale for Vertonghen's return, Wilmots added: "Based on our forecast it should be between six and eight weeks.
"He suffered the same injury before and it took about that long to recover. But it depends on his rehabilitation.
"We've been in touch with [Tottenham head coach Mauricio] Pochettino and the Tottenham doctor."
Belgium, who have been without injured captain Vincent Kompany in France, had been expected to shift Vertonghen into the centre to partner club-mate Toby Alderweireld with Jordan Lukaku coming in at left-back.
However, Vertonghen's absence may now hand an opportunity to 21-year-old Jason Denayer when Belgium face Wales in Lille.