Kick-off is scheduled for 18h00 South African time, with Eritrea hosting the Group D encounter at the Al-Salam Stadium after being unable to stage the fixture at home due to the lack of a Confederation of African Football-accredited venue.
South Africa opened their qualifying campaign with a 2-1 victory over Guinea at Orlando Stadium, giving new coach Pitso Mosimane a winning start to his latest spell in charge of the national team.
However, Mosimane has warned his players against taking Eritrea lightly, particularly after the East Africans secured a point in their opening qualifier against Kenya.
Eritrea held Kenya to a 1-1 draw at the Nyayo National Stadium in Nairobi, leaving the two teams level on one point heading into Wednesday's fixtures.
"I am happy with the result we got (in the first qualifier against Guinea), we got the result, and even the attitude was good. We need to show the same attitude against Eritrea because you can't give respect to Guinea and not accord the same to an Eritrea side that just claimed a point away from home in Kenya," said Mosimane as quoted on the SAFA website.
The Bafana coach will be hoping his side can maintain the intensity and discipline that helped them overcome Guinea as they look to make it back-to-back victories.
Captain Ronwen Williams has also stressed the importance of continuing to embrace the changes introduced by Mosimane since his return.
"The spirit and the energy amongst ourselves is always good and we have maintained that," said the Bafana skipper.
"The guys have been open to all the changes that the coach has implemented and one way to see that is through the tactical agreements we had in the previous game, to see some of the things we worked on in training ahead of the game."
With another three points at stake, Bafana will be aiming to strengthen their position in Group D and carry their positive momentum into the next stage of qualifying.