Already-qualified Egypt flew to Ghana on Friday to meet the Black Stars in their final World Cup qualifier on Sunday.
The Pharaohs meet Ghana in Cape Coast in their final Group E game, having secured their place at next year's Russia finals with one match to spare.
Egypt reached their first World Cup finals since 1990 after securing a dramatic 2-1 victory over Congo in Alexandria last month, thanks to a double from star winger Mohamed Salah that included a stoppage-time penalty.
The Pharaohs have rested Salah for the Ghana game. Central defender Ahmed Hegazi is also out for personal reasons while regular left-back Mohamed Abdel-Shafi was ruled out through injury.
Ghana will miss key duo duo Asamoah Gyan and Christian due to injury.
"We will try to test new tactics against Ghana," Egypt coach Hector Cuper said.
Ghana lie third in the group with six points, two behind Uganda who meet bottom side Congo, also on Sunday.
Egypt beat Ghana 2-0 in their previous World Cup qualifier in November 2016. The seven-time African champions defeated Ghana again at the Nations Cup early this year, with a free-kick from Salah giving them a 1-0 victory.
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