South Africa will be without Graeme Smith as they look to avoid suffering a first ever ODI series whitewash on home soil.
Former skipper Smith has been released from the squad on "compassionate grounds" and has been replaced by Henry Davids for the third and final match at Centurion on Saturday.
Batsman Davids' inclusion is a reward for his good form in domestic action and could see him make his one-day debut at the age of 33.
"Henry (Davids) has performed for us in the T20 format and this is another opportunity for him to make a contribution in the ODI squad," Cricket South Africa selection convenor Andrew Hudson said.
"He had a successful run in the Momentum One-Day Cup and this is just reward for his consistent performances."
The Proteas are also without Dale Steyn and Jacques Kallis, the pair having been withdrawn after the second one-dayer due to injury.
Paceman Steyn, who had claimed nine wickets so far in the series, including career-best figures of 6-39 on Wednesday in Port Elizabeth, was ruled out with a side strain.
All-rounder Kallis, meanwhile, has an injured finger on his right hand.
The hosts opted not to call up replacements for either of the duo; Vernon Philander or Morne Morkel are likely to come in to boost the bowling attack while there could also be a place for Wayne Parnell.
Pakistan triumphed by one-run at St George's Park in the second match having already won the series opener by 23 runs in Cape Town.
Their two victories mean they have already made history by securing a first ever series win over South Africa in 50-over cricket.
Watch South Africa play Pakistan live on Sky Sports 3 on Saturday, with coverage from 8am.