A police spokeswoman said emergency services were called to the scene on Scotland St, between Smith St and Grovers Hill Rd, about 5.02pm.
Two others were injured in the two-car crash, one remains in a serious condition and another has minor injuries.
A rescue helicopter transported both to Dunedin Hospital, she said.
Traffic was diverted for over 5 hours through Saturday evening.
The road reopened at about 10.30pm.