Iniesta, 26, pulled a muscle in his right thigh during Tuesday's 6-0 hammering of Poland.
He will miss training for a few days, and therfore may be absent for the Group H opener against the Swiss in Durban.
Iniesta's season was ruined by various muscle injuries.
He was a key element, linking midfield and attack, in Spain's Euro 2008 triumph and when Barcelona pulled off an unprecedented treble of Spanish league, cup and Champions League in 2009.
The good news for Spain is that Cesc Fabregas and Fernando Torres, both of whom finished the season with serious injuries, are on the road to complete recovery, as they showed on Tuesday by scoring late goals against Poland.
The European champions fly out to South Africa on Thursday.
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