The Sara Oval at the Tamil Union Club, where Muralitharan plays his domestic cricket, is regarded as a spinners' haven tailor-made for the prolific star.
That won't be good news for the beleaguered Proteas, already reeling under Muralitharan's 10-wicket haul in the first Test at the Sinhalese sports club (SSC) which Sri Lanka won by an innings and 153 runs.
The hosts will be further boosted on Friday by the return of experienced left-arm seamer Chaminda Vaas, who missed the first Test with a hamstring injury suffered on the recent England tour.
"Vaasy is a class act and it is great to have him back," said Sri Lankan captain Mahela Jayawardene of his leading seamer, who has captured 306 wickets at an average of 29.2.
"We missed him in the first Test because of the pressure he applies on batsmen from one end. He is a superb wicket-taking bowler."
Sri Lanka are expected to leave out Farveez Maharoof to accommodate Vaas, but leg-spinner Malinga Bandara may also be considered if the wicket promises turn early in the match.
Seasoned all-rounder Shaun Pollock returns for South Africa after opting out of the first Test following the birth of his second daughter.
Pollock, who is six wickets away from becoming the first South African to reach the 400 mark, will lend experience to a squad missing captain Graeme Smith and all-rounder Jacques Kallis because of injuries.
Pollock watched from the sidelines as Sri Lanka ran up 756-5 declared at the SSC due to Jayawardene's brilliant 374 and his world record stand of 624 with Kumar Sangakkara (287).
"With Shaun back, we will go into the Test with greater confidence," said stand-in captain Ashwell Prince, who may use Pollock as a stock bowler after giving the new ball to Makhaya Ntini and Dale Steyn.
Pollock, who is likely to replace Andre Nel, said he did not expect to reach 400 wickets in this Test but stressed that was not his main priority.
"It would be nice to get to 400 at some stage. I am not sure I can get the six here," the 33-year-old said. "It's more important to help the team do well in the match."
South Africa are looking to opening batsman Herschelle Gibbs to come good after he made 19 and 18 in the first Test to prolong his batting slump.
Gibbs, who was dropped for the home series against New Zealand in April, has averaged 26.5 in his last 14 Tests. He is now expected to deliver as South Africa attempt a series-levelling win.
There was a glimmer of hope when South Africa lasted 157.2 overs in the second innings of the first Test to make 434 after being shot out for a meagre 169 on the opening day.
South Africa (likely): Ashwell Prince (capt), Herschelle Gibbs, Hashim Amla, Jacques Rudolph, A.B. De Villiers, Mark Boucher, Andrew Hall, Shaun Pollock, Nicky Boje, Makhaya Ntini, Dale Steyn.
Sri Lanka (from): Mahela Jayawardene (capt), Upul Tharanga, Sanath Jayasuriya, Kumar Sangakkara, Tillekeratne Dilshan, Chamara Kapugedera, Prasanna Jayawardene, Chaminda Vaas, Farveez Maharoof, Lasith Malinga, Dilhara Fernando, Muttiah Muralitharan, Malinga Bandara.
Umpires: Billy Bowden (NZL) and Mark Benson (ENG)
Match referee: Javagal Srinath (IND)