The Everton midfielder withdrew from the game after pulling a thigh muscle during Saturday's 2-0 defeat by West Bromwich Albion in the Premier League.
Racing Genk full back Anele Ngcongca, who picked up an injury in his team's UEFA Europa League tie against Aktobe last week, is also missing while South Africa Footballer of the Year Siyabonga Nomvethe is a doubt.
Friday's match is the first in charge for new South Africa coach Gordon Igesund, brought in after the 2010 World Cup hosts failed to win either of their opening two qualifiers for the 2014 finals in Brazil.
- West Bromwich Albion
- Anele Ngcongca
- South Africa