The two who died were travelling on the A952 at Mintlaw, near Peterhead, Aberdeenshire, when the vehicles were involved in the collision last night.
The driver of the other vehicle was taken to Aberdeen Royal Infirmary.
Firefighters had to cut free one of those involved following the accident between a red Vauxhall Corsa hatchback and a white Corsa van. The road was closed between Mintlaw and the Cortes junction to allow accident investigators to examine the area.
Sergeant David Pirie, of Aberdeenshire road policing unit, said: "Our thoughts and condolences go out to the families of those involved at this terrible time.
"I would appeal to anyone who witnessed either of the vehicles being driven near the locus to come forward.
"I am keen to establish the full facts and circumstances to identify the cause of this tragedy."