The collision occurred at Huncoat prior to Rising Bridge around 9.45am when a silver Mercedes coupé was involved in a collision with a Mercedes Sprinter van, a red Mini Cooper and white Ford Transit pickup.
It is believed the Mercedes coupé was travelling along the southbound carriageway when it lost control and veered onto the opposite carriageway colliding with the other vehicles which were heading north towards Burnley.
Five other people were treated at the scene by paramedics for minor injuries.
Sergeant Malcolm Bell said: “I would appeal to anybody that witnessed this collision and has not yet spoken with police to please contact us.
“I would also appeal to anyone that saw the Mercedes travelling along the bypass prior to the collision to come forward.”