The 32-year-old hooker cum prop has had an operation to relieve pressure on discs in his neck and will not play again until the start of the new southern hemisphere season next year.
"This was not a career threatening injury, but the timing was right for John to undergo surgery," said Springbok team doctor Craig Roberts.
"He will now have a prolonged period of recovery in advance of the new season."
That recovery period is expected to last at least three months, with Smit hoping to be fully fit in good time for the 2011 Super 15 season which begins when the Sharks face the Cheetahs on the weekend of February 18.
It means Smit will be unavailable for a potential Grand Slam tour on which they will play all four Home Unions on successive weekends this November.
The setback also throws Smit's own international career into doubt as a successful search for a replacement front rower and captain could heighten calls for Smit to call it a day.
The Sharks skipper has come under increasing pressure as a result of the Boks' disappointing Tri Nations showing in which they won just one of six games and finished bottom of the table.