Commuters could face long delays because of major refurbishment work on the A27.
The road will be closed at night and will have speed restrictions and narrow lanes because of maintenance work on Southerham railway bridge, near Lewes.
Temporary traffic lights and a 40mph speed limit will also be in place from 9.30am to 4pm between Beddingham and Firle throughout May.
And the Southwick tunnel will be closed overnight twice.
There was traffic chaos in March when roadworks at the Crossbush junction, near Arundel, caused severe tailbacks and led to the Highways Agency apologising and altering the layout of the works.
Yesterday officials warned that bad weather could push the delays beyond the jubilee weekend.
From today the A27 will have roadworks on it between the Ashcombe and Southerham roundabouts as staff waterproof Southerham railway bridge.
The structure was refurbished in February but poor weather meant the waterproofing could not be done.
A spokeswoman said the nature of the work meant it could not be carried out solely at night due to the humidity.
On May 17, 18 and 21 there will be narrow lanes and a 40mph speed limit between 5am and 9pm which could cause major tailbacks during rush hour. The westbound carriageway will be shut between the roundabouts this weekend, with a one-lane contraflow system in place.
Carl Maynard, East Sussex County Council’s cabinet member for transport, said: “In terms of these major works it would be preferable if possible to do it all overnight but if it is necessary then you want to minimise disruption.
“I am surprised they are doing works to the bridge so soon after opening it.”
Steve Percy, of the People’s Parking Protest motoring group, said: “It will have a massive impact but there is no way to avoid it because it is a major route for people. When you are messing with thousands of people’s journeys it is not funny.”
Bala Vishnubala, from the Highways Agency, said: “This work will prolong the life of the bridge on this vital south coast route and help to reduce the risk of unplanned closures for maintenance work in the future.
“We have listened to local concerns about the impact of the work on traffic, and have carefully planned it to ensure two lanes are open in both directions at peak times Monday to Friday.”
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