The 28-year old Niekerk sustained a fracture on her left ankle after accidentally slipping on a wet surface at home last week.
"South African captain, Dane van Niekerk has sustained a left ankle fracture in the last week, ruling her out for a minimum of three months and will be unavailable for the training camp, West Indies tour and the 2022 ICC Women's Cricket World Cup hosted in New Zealand from March 4," the CSA said in a statement.
CSA has not named a replacement captain ahead of their training camp which starts on Friday before the four-match ODI series against West Indies in Johannesburg between January 28 - February 6.
"As things stand, she doesn't require surgery but will be monitored closely. It's a stable fracture with minimal displacement and her recovery timeline is no less than 12 weeks," team doctor Tshegofatso Gaetsewe said.
The South African board has named a group of 21 players for the camp, including senior names Shabnim Ismail, Marizanne Kapp, Ayabonga Khaka and Lizelle Lee, among others. CSA also picked uncapped Western Province batter Delmari Tucker and gave another chance to Raisibe Ntozakhe.
The extended squad will enter a bio-secure environment on Friday, and will be pruned further for the ODIs following a 10-day training camp.
"Losing Dane is massive for the team and the country, we will sorely miss her leadership and all-round cricket abilities. I would like to wish her all the best with her recovery and a smooth and seamless return to the national team," Convenor of Selectors, Clinton du Preez said.
"This brings about an opportunity for another player within the pipeline," he added.
Training squad: Anneke Bosch, Tazmin Brits, Trisha Chetty, Nadine de Klerk, Mignon du Preez, Lara Goodall, Shabnim Ismail, Sinalo Jafta, Marizanne Kapp, Ayabonga Khaka, Masabata Klaas, Lizelle Lee, Sune Luus, Nonkululeko Mlaba, Raisibe Ntozakhe, Tumi Sekhukhune, Nondumiso Shangase, Andrie Steyn, Chloe Tryon, Delmari Tucker, Laura Wolvaardt