This story has been updated. For the latest information, click here.
UPDATE: 4:50 a.m. Wednesday
CHP says all lanes on Highway 101 at the Cuesta Grade are now open.
UPDATE: 12:35 a.m. Wednesday
CHP is opening one lane on Highway 101 Southbound.
A major emergency response was underway late Tuesday on the Cuesta Grade following a deadly crash.
The California Highway Patrol shut down both directions of Highway 101 before reopening one northbound lane.
CHP reports it began with a crash on southbound Highway 101 at Cuesta Springs Road just before 11 p.m. Tuesday.
According to CHP, four victims were involved in the crash. They were all in a car that hit the center divider. Two of the people were ejected and died at the scene. They had not been wearing seatbelts, according to CHP. Officers say two other victims were taken to the hospital with minor to moderate injuries.
At least one additional vehicle became involved after hitting one of the ejected victims on the highway.
CHP reopened one northbound lane of 101 around 11:35 p.m. The southbound lanes are shut down at Highway 58. Drivers in the area who are looking to travel southbound through San Luis Obispo County should take Highway 41 to Highway 1 as a detour around this crash scene.
CHP estimates the highway closure will last up to five hours.
CAL FIRE SLO, San Luis Obispo City Fire and Santa Margarita Fire departments responded with five engines and expected to be at the scene into Wednesday morning.
This is a developing story. We will update this page as more information comes into the KSBY Newsroom.