Coach Stephen Keshi made the announcement at a media conference on Tuesday but added that Victor Moses, Obi Mikel's Chelsea club mate, would return to the side after missing June's Confederations Cup in Brazil because of injury.
Obi Mikel joins new Fenerbahce signing Emmanuel Emenike, goalkeeper Victor Enyeama and 19-year-old centre back Kenneth Omeruo on the sidelines.
Wednesday's match against South Africa at the Moses Mabhida Stadium is a warm-up for both countries before key World Cup qualifiers next month.
Nigeria were surprise Nations Cup winners at the tournament in South Africa in January and February.
- Sports & Recreation
- Obi Mikel
- Victor Moses
- Emmanuel Emenike
- Stephen Keshi