Jonny Wilkinson will not be considered for England's Six Nations Championship finale against Wales in Cardiff on Saturday.
England say the Newcastle fly-half is making "good progress" from a hamstring problem that ruled him out of the 26-18 victory over France two days ago.
But he will not have completed his rehabilitation in time for the Millennium Stadium encounter, which could see England crowned Six Nations champions if they win.
Wilkinson's Newcastle colleague Toby Flood is expected retain the number 10 shirt after an impressive full debut against France, although he is currently battling to overcome a leg injury.
Wilkinson will now have missed 32 of England's 35 Test matches since the 2003 World Cup final triumph in Sydney.
He proved his fitness to face Ireland last month barely 12 hours before kick-off, but his England career is now on hold until the two-Test tour of South Africa.
England meet the Springboks - who are also their pivotal World Cup pool opponents - in Bloemfontein on May 26, and then in Pretoria seven days later.
England, meanwhile, have called up uncapped Wasps back-row forward James Haskell to their training squad at Bath University.
Harlequins number eight Nick Easter, who produced an impressive performance against France, complained of neck pain on Monday.
He is being treated by the England medical staff and will not train for the early part of this week.
Skipper Mike Catt has had treatment on his left hamstring but should train in the next couple of days.
Catt's midfield colleague Mike Tindall has already been ruled out of the Wales game due to a suspected knee infection, with Newcastle's Mathew Tait the favourite to replace him.
Injuries permitting, that is anticipated to be the only change when England head coach Brian Ashton announces his line-up.