The 28-year-old will have surgery next Tuesday after a specialist recommended that an operation would be the best course of action to cure a longstanding problem.
Du Preez will definitely miss the Tests against France and Italy as well as the entire Tri Nations campaign after being ruled out for around six months.
Having played in all three Tests against the Lions last summer, du Preez was expected to renew acquaintances with Mike Phillips when South Africa face Wales in November as part of a Grand Slam tour that will feature matches against all four Home Nations.
But that match up is now unlikely to take place either, with du Preez set to be continuing his rehab back in South Africa while his colleagues tour the northern hemisphere.
That means that Scottish Lions Mike Blair and Chris Cusiter, Ireland's original 2009 Lions selection Tomas O'Leary and England's most recent Lion Harry Ellis or possible future tourists Danny Care and Ben Youngs won't have the chance to test themselves against the man widely regarded as the best No9 in world rugby.
Du Preez and the Springbok medical team hope the decision to opt for an operation will give the double Super 14 winner the best chance of recovering top form in time for the 2011 World Cup in New Zealand.