The four-car pileup was reported shortly after 1:30 a.m. at the intersection of Gilman Springs and Eden Hot Springs roads, according to officials with the California Highway Patrol.
Cal Fire officials reported that one vehicle went over an embankment. Two people trapped in the wreckage had to be extricated, CHP officials said.
In total, nine people were taken to the hospital - three of them in critical condition.
CHP officials said the collision was being investigated as a possible DUI crash.