Diversions are in place to allow emergency services to deal with the crash on the A66 at Threlkeld, near Keswick.
Travelling towards west Cumbria, motorists are advised to use junction 41 of the M6, travelling along the B5305, Wigton.
Travelling towards Penrith, motorists should follow the diversions in place at the Crossthwaite roundabout, Keswick.
Cumbria Police say that the road will be closed for some time.
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