Police have warned the A4 Portway will remain closed for hours while vehicle recovery work is carried out.
Avon and Somerset Police have issued a new statement after the fatal crash near Sea Mills at around 5.45am.
Police confirmed at lunchtime that the male motorcyclist suffered significant injuries. He was pronounced dead at the scene and his next of kin has been informed.
Read more: Updates as fatal crash closes A4 Portway
The road which links Avonmouth and Bristol is shut from the A4162 at Sylvan Way, Sea Mills, to the A4176 Bridge Valley Road at Clifton Downs.
Specialist collision investigators have arrived at the scene.
Police said in the latest statement: "One person has died in a collision on the A4 Portway this morning (Thursday, October 7).
"The incident, involving a motorbike and a lorry, occurred near Sea Mills at approximately 5.45am.
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"Police, ambulance and fire crews were all called to the scene.
"Sadly, the male motorcyclist sustained significant injuries and was pronounced dead at the scene. His next of kin have been informed.
"Collision investigators have attended to examine the scene. The road is expected to remain closed for the next few hours while vehicle recovery work is carried out."
Police request any witnesses who have not yet spoken to police to call 101 and give reference number 5221233777.
