A female driver, 63, and a male passenger, 60, were killed when their Holden ute rolled while travelling on the Stuart Highway at Mount Willoughby at 11am on Friday.
The highway was closed between Marla and Coober Pedy while major crash officers investigated the scene.
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It has since been reopened.
The deaths mark the 55th and 56th lives lost on South Australian roads this year, compared to 33 at this time last year.