Junctions 23A and 24 of the M1 in Leicestershire will be closed from 22.00 on Friday until 15.00 on Sunday.
The diversion, which was announced in March, is taking place to enable a bridge to be installed for the new Kegworth bypass.
The closure is expected to cause delays for travellers using East Midlands Airport this weekend, as well as Fulham FC fans heading south after their team’s away match against Derby County at the Pride Park Stadium on Friday night.
Tom Greatrex, chairman of the Fulham Supporters Trust, told the BBC it would make more sense if the road was closed an hour later.
“It’s not Highways England’s fault as the game has been scheduled at short notice on a Friday night, but I thought it might make a bit of sense to avoid a whole load of chaos by starting an hour later,” he said.
“The closure is going to start at 10 o’clock and at about quarter to ten, roughly, there will be about 30,000 other people coming out of the Derby ground.
“I would expect a chunk of those would normally be heading towards the M1 by car.”
A spokesperson from Segro, which is leading on the project, said: “Given the high level of planning and coordination involved in this project, we regret that we can't change the timings this close to start of the operation.
“We apologise for any inconvenience caused.”
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