The crash, also involving a big rig and sedan, happened at about 9:30 p.m. near Arrowmill Avenue and Washington Boulevard.
Three people from the red sedan were extricated and transported to a nearby hospital in critical condition.
It's unclear what caused the collision, but speed may have been factor. Pieces of the sedan were spotted wedged underneath the big rig, which remained at the scene.
Sheriff's deputies were holding the scene as a possible crime scene.