Ayew has contracted coronavirus and will most likely be replaced in the squad. His senior brother, Andre Ayew, has been ruled out due to suspension.
On Sunday morning, the Crystal Palace striker was not even selected on the bench as the Eagles hammered Everton 4-0 to reach the FA Cup semi-finals.
Ayew is a vital player, and his absence could jeopardize the team's chances of defeating Nigeria.
Semenyo suffered a knee injury while playing for Bristol City against West Brom in the English Championship.
The attacker, who was given his first call-up for the vital match, was replaced after only six minutes, and Bristol manager Nigel Pearson claims the player is furious.
"At the moment, I don't know [the extent of the injury], but clearly he [Antoine Semenyo] is angry because he's been called up for the Ghana squad, and he's jarred his knee, so we'll have to see how he is." I can’t offer you any more than that at the moment,” Bristol manager Nigel Pearson said.
As the technical team prepares to address the nation on Monday morning, these two players could be changed.
Tuesday is supposed to be the start of the Black Stars' preparations for the two games. They'll fly to Kumasi for two training sessions before the first leg on March 25.
The second leg will take place at the Moshood Abiola National Stadium in Abuja four days later.
The champion will play in the World Cup in Qatar later this year.
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