Temporary traffic lights will be installed on the A66 near Keswick for five days.
Drivers are urged to plan ahead and allow extra time as delays are expected.
National Highways said it would be carrying out waterproofing and resurfacing work on the Threlkeld bridge, from 8pm on Sunday September 21 to noon Friday September 26.
Temporary two-way traffic lights will be in place and a 30mph speed limit will be in place either side of the bridge.
National Highways said it will work for 24 hours a day to make sure the work is finished before Saturday September 27.
