The Stormers' skipper lasted just seven minutes of his side's 34-11 Super 14 defeat to the Hurricanes in Wellington before badly tearing his groin.
"I will go for scans, but I definitely won't play next weekend. At this stage you just hope for the best," said a disconsolate de Villiers.
"I just hope I will still be considered for selection by the time they pick the Springbok squad. I will have to reassess it all on Monday."
Things went from bad to worse for the 2008 South African Player of the Year as he saw his side slip to their seventh defeat in 10 games in the Super 14 and slip to 12th place. His departure also made life easier for his opposite number, Ma'a Nonu, he helped himself to two tries in the game.
The Stormers move on to the south island to face the Highlanders in their final tour match this weekend knowing that their Super 14 campaign is all but over once again.
Coach Rassie Erasmus has suffered from horrendous injury problems this season and will also be missing Test prop Brian Mujati this weekend after he was concussed.
But it will be the loss of de Villiers, rated as the best centre in the world, that will concern Erasmus, and Springbok coach Peter de Villiers, most of all.
It turned into a miserable weekend for the South African sides in the Super 14 with only the Lions winning. Their 31-11 triumph over the Reds in Brisbane stood out like a beacon in Round 10 as the Chiefs put the Cheetahs to the sword, 28-10, to move to the top, the reigning champions the Crusaders pipped the Sharks 13-10 in Durban and the Brumbies edged the Bulls 32-31