The crash happened on Highway 41 near Avenue 14 early Monday morning.
The California Highway Patrol says a big rig going northbound on Highway 41 tried to make a u-turn when the driver missed his exit.
The CHP says the big rig pulled out in front of on-coming traffic and the driver of a van wasn't able to stop in time.
The two people inside the van were taken to the hospital. Their conditions have not been released.
The accident temporarily blocked a portion on Highway 41, but all lanes were back open by midday.
