Etzebeth, 31, missed the title-holders’ crushing 76-0 victory over Romania last weekend, having picked up the injury against Scotland the week before.
Head coach Jacques Nienaber has made 13 changes to the side that dismantled Romania, reverting to 14 of the 15 players who started against Scotland.
The only change compared to that match sees Bongi Mbonambi take the place of injured hooker Malcolm Marx.
“Ireland are a quality team with a strong pack of forwards and talented backs, and they play with a lot of speed, so we know what we have to do to deliver a top-drawer performance for things to go our way,” Nienaber said.
“We faced them late last year and we’ve been keeping an eye on their performances this year, so everyone knows what we have to do this weekend,” he added.
After playing world number one side Ireland on Saturday in Paris, the Springboks will end their Pool B campaign against Tonga on October 1.
South Africa (15-1)
Damian Willemse,; Kurt-Lee Arendse, Jesse Kriel, Damian De Allende, Cheslin Kolbe; Manie Libbok, Faf de Klerk; Jasper Wiese, Pieter-Steph Du Toit, Siya Kolisi (capt); Franco Mostert, Eben Etzebeth; Frans Malherbe, Bongi Mbonambi, Steven Kitshoff
Replacements: Deon Fourie, Ox Nche, Trevor Nyakane, Jean Kleyn, RG Snyman, Marco van Staden, Kwagga Smith, Cobus Reinach
Coach: Jacques Nienaber (RSA)
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