The 25-year-old has an ankle injury and missed the final Test of the recent series against Pakistan.
It has been suggested that bowler Steven Finn would also miss the tour with a foot injury but he has said he still hopes to be involved.
Chris Woakes, Liam Plunkett, Chris Jordan and Mark Footitt are options to replace Wood in the 17-man squad.
James Anderson and Stuart Broad will be England's frontline pace bowlers in the squad, which will be announced on Thursday morning.
The tour gets under way on 15 December with a warm-up game against a South African Invitational XI and runs through to 21 February 2016.
England will play four Tests, five one-day internationals and two Twenty20s.
All-rounder Ben Stokes is understood to have recovered sufficiently from a "collar bone joint injury" and should be fit for the tour.
The 24-year-old suffered the injury fielding in the final Test of the 2-0 series defeat by Pakistan in the United Arab Emirates this month.

On Monday, Rick Maddison fatally shot Senior Constable Brett Forte after the police officer intercepted his car in Queensland.
He fled to a nearby farmhouse and spent the night in a stand-off with police.
Maddison was killed by authorities after fleeing the house and firing on police, Queensland Police Assistant Commissioner Tony Wright said.
"He has been challenged by police at that point in time - he has fired at those police," he told reporters on Tuesday.
"Specialist police have returned fire. The male person has been shot and that male person has been declared deceased at the scene."
Mr Forte was killed after intercepting Maddison, who police had described as a "wanted person", about 14:20 local time (04:20 GMT) on Monday.
Authorities had set up an exclusion zone around the farm and began negotiating with Maddison at midnight.
The confrontation happened just after 11:00.
On Monday, Queensland Police Commissioner Ian Stewart said he wanted to resolve the siege "as peacefully as humanly possible".
Residents nearby residents were ordered to evacuate their homes on Monday evening.
Mr Forte was a husband and father who had been a police officer for more than 15 years, authorities said.
"It is so distressing - not just to the police service - but to the community, that we have lost a fine police officer," Mr Stewart said.
Queensland Police Union president Ian Leavers said the officer was shot "simply trying to apprehend a wanted person".
"It could have been any one of us anywhere in Australia," he told the Seven Network.
"Our thoughts are with his wife and his three children. He has got a daughter and two sons."

2 May 2015 Last updated at 10:24 BST
One of the top things many voters want politicians to do is to protect the National Health Service (NHS).
But why do people think it's so important?
Martin's been to the Great North Children's Hospital in Newcastle to find out.
England pace bowler Mark Wood looks set to miss this winter's tour of South Africa because of injury.
[NEXT_CONCEPT]
A man who killed a policeman before holding authorities at bay for 18 hours has been shot dead in Australia.
[NEXT_CONCEPT]
On May 7 it's the general election, where adults across the country will decide who they want to run the UK.