Drivers have been told to only travel if necessary as a section of the M25 in Surrey will be shut this weekend.
The closure is to allow for ongoing improvement works, with the potential for long delays and congestion for motorists.
The motorway will be shut between junctions nine (A243 Leatherhead) and 10 (A3 Wisley) from 21:00 BST on Friday until 06:00 on Monday.
Senior project manager Dan Kittredge urged motorists to only travel “if absolutely necessary”.
A five-mile (8km) stretch of the M25 was shut in March between junctions 10 and 11 – the first time there had been a scheduled daytime shutdown of all lanes since the motorway opened in 1986.
This weekend’s closure will allow a new bridge consisting of 68 beams, each weighing 16 tonnes, and a further four beams weighing 40 tonnes to be installed, National Highways said.
Four diversion routes will be in place between Gatwick and Heathrow, two in either direction for regular traffic and two for overheight vehicles.
Despite the closure, drivers have been told by the government agency to “continue to come to Surrey”.
Senior project manager Jonathan Wade said: “Surrey is an enormous county so please carry on as you are.”
The improvement scheme, which forms part of a £317m upgrade to the motorway, will see an increase in the number of lanes to attempt to make journeys safer and a new junction layout to improve traffic flow.
A further three closures are planned before the end of the year, with the next one scheduled for August.