Botha, a pivotal figure in the Springboks' front-five, is struggling to overcome an Achilles problem and South Africa assistant coach Dick Muir confirmed it is unlikely that 74 times-capped Botha would make the starting XV.
"We are a little bit worried about Bakkies - he is our major concern," said Muir.
"It's his Achilles, and being a big man he obviously takes a lot of pressure in that area.
"He's so important for us for the remainder of the competition that we wouldn't take any chances with Bakkies.
"We will take it week by week - but I think he is going to be out this week unfortunately."
Danie Rossouw would be Botha's probable replacement, although there has also been a concern about lock Victor Matfield, whose hamstring niggle restricted his training during the early part of this week.
Springboks coach Peter de Villiers and his Wales counterpart Warren Gatland are due to name their starting line-ups for the Pool D encounter on Friday.
Gilbert has released a new line of rugby cleats. The Gilbert Virtuo 8S is part of the exciting new product. Check it out.
The entire All Blacks apparel line has been updated for 2013/14. Check out the New Zealand All Blacks polo.
The Nike Tiempo is a solid rugby cleat and one of few styles still made from full-grain natural leather.
The Gilbert Blitz 8S rugby cleat is a great cleat at a great price of $69.99. Get a new pair of cleats today.
A cool looking all black rugby cleat with the high performance adidas is known for. Get in the Gear!
Wear the crest of the British and Irish Lions on your t-shirt. A great look for the summer.
$29.99
The All Blacks Performance t-shirt is black with hints of blue from the training jersey. Very Cool.
The New Zealand All Blacks training jersey for 2013/14. Get in the Gear!
The USA Rugby Pro Alternate rugby jersey is perfect for any fan of the Eagles. Get yours to wear during the summer Test matches.
The NEW All Blacks 2013/14 jersey has arrived at World Rugby Shop. Dare to wear the colors of the All Blacks.