Egypt were held to a goalless draw by Angola at Cairo International Stadium on Friday in their opening qualifier.
Salah, who joined Turkey's Trabzonspor from Liverpool recently, started against Angola but did not complete the match after coach Hossam Hassan substituted him midway through the second half.
"The Egypt national team's technical staff, led by Hossam Hassan, has decided to rest Mohamed Salah for the match against South Sudan scheduled for September 29th because of the playing surface," EFA said on social media.
"It was agreed between the national team's technical staff and Mohamed Salah before the Angola match that he would not play against South Sudan, and the technical staff preferred this approach in order to protect the player," EFA added.
The match between South Sudan and Egypt will be played at Juba Stadium, which has an artificial turf surface.