The two pedestrians were hit by a Ford Explorer driven by a 32-year-old woman travelling east through the intersection at Kingsway and Joyce Street at around 11:20 p.m. PT, say police.
The police collision investigation unit is still attempting to determine the cause of the crash, but one witness told CBC News the vehicle appeared to run a red light.
"Although it is still early in the investigation, indications are that the pedestrians were crossing on a green light," said Const. Brian Montague.
The vehicle appeared to remain at the scene after the accident, but no charges have been laid.
Police have not released the names of the victims.
The incident is Vancouver's 10th pedestrian fatality of 2012, and the 18th traffic-related fatality.