Mohamed Salah will miss Egypt's vital Africa Cup of Nations Group B game against Cape Verde on Monday with a hamstring injury.
The Liverpool forward, 31, has also been ruled out of a last-16 tie should Egypt qualify.
Salah limped off before half-time in the 2-2 draw with Ghana on Thursday.
The result has left the record seven-time African champions needing to beat the already-qualified Cape Verde to guarantee their progression.
"Tests on Mohamed Salah, the captain of the Egypt national team, proved that he suffered a hamstring injury and will miss the next two matches of the team at the Afcon," the Egyptian Football Association said.
Salah will therefore only feature in the tournament again if Egypt advance to a quarter-final on 2 or 3 February.
Earlier on Friday Liverpool boss Jurgen Klopp suggested Salah's hamstring problem was likely to be severe, given the forward had missed just 10 league games for the Reds in more than six seasons.
"He was shocked and couldn't see why he was hit by something so intense," said Klopp.
"You have these hamstring injuries in a different way. He felt it and we know how rarely Mo goes off, or needs to go off, so it is definitely something."
Losing Salah, who is on the cusp of 100 caps for his country, comes as a major blow to Egypt, who have made a sluggish start to their campaign in the Ivory Coast, collecting two points from two matches.
Salah scored a last-gasp penalty on Sunday, after a VAR decision, to help Egypt draw 2-2 with Mozambique to avoid an embarrassing opening defeat, and they also twice had to come from behind against Ghana.
The last of Egypt's seven titles at the Cup of Nations came in 2010, a year before Salah made his international debut.