Manx Utilities says motorists face six months of misery as it improves the capital's sewage system.
Work on a 23-week project on the Old Castletown Road will start on Thursday.
Kewaigue's pumping station will be replaced, and work will take place on the Old Castletown Road and Heron & Brearley brewery site.
There'll be a number of road closures and traffic restrictions between Thursday, April 3 and Wednesday, April 16.
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Bus Vannin releases this Sunday's strike schedule
MHK wants changes to tax laws for couples
What does it take to close roads?
Firefighters called to fire at tip this morning
Airport recruiting for firefighters
Northern roads to close for half marathon this weekend
City centre street to close for two days