Police said about 9.30am they were responding to a crash at the intersection of Taieri Mouth and Dicksons Rds, at Kuri Bush.
A vehicle with two people inside had rolled down a bank, police said.
One person was airlifted to Dunedin Hospital in critical condition, while the second was taken to hospital by ambulance in a moderate to serious condition.
Police initially said one person had been seriously injured.
The road was closed for several hours but police advised around 3.15pm it had reopened.