The M6 will be closed northbound from junctions 39 to 40 this weekend.
On Sunday, the section of road northbound between Shap and Penrith will be closed from 8pm on Sunday September 21 to 6am on Monday September 22.
The road is closed so repairs can be carried out on Lowther Bridge.
A diversion will be in place via the A6 during the closure and people are asked to allow more time for their journeys.
National Highways said: “A lot of the work we’re doing is underneath the carriageway, where it’s not visible to drivers.
“We’ve started installing a system that helps protect the bridge from long term damage.
“To give our teams safe access, we’ve built a large scaffolding structure under the bridge. This lets us carry out repairs while keeping traffic moving above.”
The road will also be closed northbound from 8pm on Saturday September 27 until 6am on Sunday September 28 and southbound from 8pm on Sunday September 28 until 6am on Monday September 29.
