The QEII Bridge, part of the Dartford Crossing, will shut between 10.30pm on Saturday (June 6) and 5.30am on Sunday (June 7), according to National Highways.
The closure will allow for bridge maintenance works, with the entry slip road at junction 31 of the M25 also shut as a result.
The east tunnel of the Dartford Crossing, normally used by traffic travelling anticlockwise from junction 1A to junction 31, will instead be used as a diversion for bridge traffic between 10pm on Saturday and 5am on Sunday.
The west tunnel will be open as normal for anticlockwise traffic, but has a height restriction of 4.8m.
The Dartford Crossing, also known as the A282, connects Kent with Essex and serves as a vital transport link for drivers across the south east.
It is made up of the QEII Bridge and two tunnels, joining up directly at both ends with the M25 orbital route.
The closure this weekend is part of a wider programme of maintenance works being carried out by National Highways, including cable stay refurbishment on the bridge, the replacement of tunnel panels and upgrading CCTV and lighting.
Upcoming closures include the east tunnel overnight between June 8 and June 11, followed by a series of closures on the west tunnel.
