Hosts entertain South American opposition in Pretoria.
South Africa coach Carlos Parreira is likely to recall experienced left-back Tsepo Masilela to the starting line-up in the only expected change. He replaced Lucas Thwala in the second half against Mexico.
Uruguay will be without Nicolas Lodeiro, who was sent off in the draw with France, but he was not expected to start anyway. Coach Oscar Tabarez will play with three forwards, with Edison Cavani replacing midfielder Ignacio Gonzalez. Diego Forlan is expected to drop deeper and play behind Cavani and Luis Suarez.
One booking from suspension: Dikgacoi, Masilela (South Africa); Victorino, Lugano (Uruguay). (BBC Sport)
South Africa won over a lot of neutrals with a committed display against Mexico and in a group which is set to be very tight this match could be crucial to both sides hopes of qualification. Uruguay battled hard against France but failed to put real pressure on the opposition goal and Diego Forlan and Luis Suarez will hope for more luck against the hosts in Pretoria.
Highlights of both sides first group games.
South Africa 1-1 Mexico
Uruguay 0-0 France