The A40 will be closed from Saturday night until Sunday morning as part of the £4.4m scheme to replace the Wolvercote Viaduct.
The road will be shut between the A44 junction and Cassington Village from 10pm until 7am Sunday morning.
Instead drivers will be diverted southbound on the A34 from Peartree junction to take the A420 at Botley via Eynsham and back onto the A40 via the B4449 northbound.
During the works there will also be a single lane closure on the A34 southbound.
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