Cape Town - Imran Tahir will have to wait until at least Sunday before making his debut for SA after being omitted for the fourth ODI in Port Elizabeth on Friday.
Proteas skipper Graeme Smith won the toss and elected to bat.
South Africa made two changes to the team that lost in Cape Town on Tuesday, with Morne van Wyk and Robin Peterson replacing Colin Ingram and Wayne Parnell.
India made a single change, with Parthiv Patel taking over from Murali Vijay.
India are yet to win a match at St George's, having lost all four previous encounters at the ground.
India lead the five-match series 2-1.
India - Parthiv Patel, Rohit Sharma, Virat Kohli, Yuvraj Singh, Suresh Raina, Yusuf Pathan, Mahendra Singh Dhoni (capt, wk), Harbhajan Singh, Zaheer Khan, Ashish Nehra, Munaf Patel
South Africa - Graeme Smith (capt), Hashim Amla, Morne van Wyk,
AB de Villiers (wk), JP Duminy, Faf du Plessis, Johan Botha, Robin
Peterson, Dale Steyn, Morne Morkel, Lonwabo Tsotsobe