Police confirmed a man had died in the crash on the Riverton- Wallacetown Highway at the Oreti River Bridge.
A woman critically injured in the crash died this afternoon after she was flown by rescue helicopter to Dunedin Hospital.
The crash occurred at 1.30pm, near Taramoa Rd and Price Rd, a police spokeswoman said.
The man died at the scene and the woman was transported to Dunedin Hospital in a critical condition.
She died in hospital a short time later, police said.
Emergency services at the scene said it appeared the motorcycle and a Fonterra milk tanker had collided.
A Fonterra spokeswoman confirmed a truck from the company was involved in the crash and said the driver was not injured.
"We are supporting our driver and we are assisting the police with their investigation in any way we can."
She would not be able to provide any further comment.
The road is expected to remain closed for some time while the Serious Crash Unit attends the scene.
The road remains closed between Cumnock St and Taramoa Rd.
Motorists should expect delays, take an alternative route or delay travel through the area.
A Fire and Emergency New Zealand spokesman said that two fire appliances had been sent to the scene, from Wallacetown and Invercargill.
Firefighters were helping at the scene, including with traffic control, and police were heading the operations, the spokesman said.
At least four police cars were present and it appeared the road would be blocked for some time.
