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.
England pace bowler Mark Wood looks set to miss this winter's tour of South Africa because of injury.