Star batsman Mohammad Yousuf will be back in the team after missing Pakistan's seven-wicket defeat in the first Test at Centurion because his wife was having a baby, while Umar Gul and Shoaib Akhtar could both strengthen what was a disappointing bowling line-up.
Yousuf made a world record 1788 runs in a calendar year in 2006 at an average of 99.33 and completes a world class trio for Pakistan with Younis Khan and captain Inzamam-ul-Haq in the three to five batting positions.
Inzamam said he expected Gul to have recovered from an ankle injury. The fast bowler was a key figure in Pakistan's series win over the West Indies in November.
If fellow fast bowler Shoaib Ahtar is included, Pakistan will field four of the top 20 bowlers in the latest ICC Test rankings, together with Mohammad Asif and leg-spinner Danish Kaneria.
The inability to sustain pressure on the South African batting when Asif and Kaneria were not in action in Centurion was a major factor in South Africa taking a 1-0 lead in the three-match series.
South Africa are likely to field an unchanged team, with fast bowler Dale Steyn still struggling with a thigh strain.
There has been discussion, however, about the possibility of rotating the South African fast men to give Makhaya Ntini and Shaun Pollock a break before the World Cup in the West Indies in March.
South African captain Graeme Smith said he would prefer to pick the strongest possible team at all times but added: "You've got to be realistic in terms of the season. The bowlers have had a huge workload on wickets that haven't been too helpful."
Pitches have been a source of frustration to the South Africans this season, with their wins over India in Cape Town and Pakistan at Centurion achieved on surfaces which did not have the pace and bounce which has been one of the main advantages for South African teams playing at home.
Port Elizabeth traditionally has one of the slowest pitches in South Africa. Only one first-class four-day match has been played at St George's this season and slow bowlers did much of the bowling in a match which had a high-scoring first innings before the bowlers had the upper hand the second time around.
South Africa will go into the match high on confidence after winning three matches in a row.
Their top order batting, which was a concern earlier in the season, has been reasonably solid lately, although opening batsman AB de Villiers has yet to make a half-century in four home Tests this season.
Herschelle Gibbs, who made an impressive 94 in the first Test against Pakistan, is expected to play after lodging an appeal against a two-Test ban for making remarks picked up by a stump microphone that match referee Chris Broad said were "racially offensive."
South Africa: Graeme Smith (capt), Jacques Kallis (v-capt), Paul Adams, Hashim Amla, Mark Boucher (wk), AB de Villiers, Herschelle Gibbs, Andrew Hall, Paul Harris, Mornorkel, Andrel, Makhaya Ntini, Shaun Pollock, Ashwell Prince, Jacques Rudolph and Dale Steyn.
Pakistan: Inzamam-ul-Haq (capt), Mohammad Hafeez, Imran Farhat, Yasir Hameed, Younis Khan, Mohammad Yousuf, Asim Kamal, Faisal Iqbal, Kamran Akmal (wk), Zulqernain Haider, Shahid Nazir, Umar Gul, Mohammad Asif, Mohammad Sami, Danish Kaneria, Rana Naved-ul-Hasan and Shoaib Akhtar.
Umpires: Billy Doctrove (WI), Peter Parker (Aus) and TV umpire: Rudi Koertzen (RSA).
Match referee: Chris Broad (Eng).