Update: 6:40 p.m.
Caltrans is reporting that all southbound lanes of Highway 101 near the Los Osos Valley Road exit are open.
According to the California Highway Patrol Traffic Incident Information Page, at least a motorcycle and pickup truck were involved in the crash.
An ambulance was called to the scene to assist with major injuries, the CHP Traffic Incident Information Page said.
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One lane of southbound traffic on Highway 101 north of the Los Osos Valley Road exit is blocked by a multi-vehicle crash, Caltrans said on its Twitter account about 5 p.m. Wednesday.
Caltrans said to expect long delays and use Highway 227 as an alternate route.
The CHP is on scene investigating the incident.
This story will be updated as more information becomes available.