Defender Shehu Abdulahi, goalkeeper Francis Uzoho and striker Odion Ighalo are sidelined by injury, while Leicester City midfielder Wilfred Ndidi is suspended.
“This will be the most difficult match for this young team,” Rohr said.
“It’s more than a year since we played against South Africa and lost in Uyo.
“It’s a different team now with the experience of the World Cup and my young team will do a good match even if we’re missing four important players especially our goal scorer and goalkeeper.”
He added: “This young team can do very well, they have big motivation and we want to win.
“It’s an opportunity for them to step up and prove what they can do. They will fight and give their best.”
Villarreal youngster Samuel Chukwueze and Olamilekan Adeleye, who feature in the domestic league, are in line for official debuts.
The three-time African champions, who arrived in South Africa early Friday, are top of Group E with nine points from four matches, while South Africa are second on eight points.
A point will be enough to secure Nigeria’s qualification for next year’s African Cup of Nations, while Bafana Bafana may need to win to guarantee their qualification.
Libya, who have four points, take on bottom team Seychelles also on Saturday with only the top two teams advancing to next year’s AFCON in Cameroon.
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