After removing a staggering two tonnes of litter from the westbound side of the A27 in May, Lewes District Council's Environment First team will be back in action next week clearing the eastbound carriageway between Falmer and Beddingham.
The overnight work will begin at 9pm on Monday and take four nights to complete. Lane closures will be in force to ensure the rubbish can be removed safely.
Signs will also be installed against motorists to take their rubbish home and that cargos on trade vehicles are safely secured.
Councillor Julie Carr, Cabinet member for Recycling, Waste and Open Spaces, said: "I'm very proud of the work our Environment First team are doing on the A27 and I implore drivers and their passengers on the A27 to behave responsibly and take their litter home. Rest assured, if we can identify litter louts we will track them down and prosecute them."