Shoprite bosses say they can't continue to trade in the centre of Douglas against a "backdrop of declining demand".
It follows news that the Chester Street store – and the Subway outlet - will close on Saturday.
Employees will be redeployed across the company and the Subway will be relocated.
Andrew Thomas is the Chief Executive of Isle of Man Enterprises: "Our employees at Chester Street have continued to work tirelessly to serve our customers, despite so many issues outside of their - and our - control, that have negatively impacted the performance of this store."
The company says it's worked with the landlord – the Department of Infrastructure – since 2011 to agree a new lease.
However Mr Thomas says it wasn’t meant to be: "This closure comes at the end of a long lease where there has been little proactive investment in the fabric of the centre, the car park and the wider centre during the time that we have held the lease.
"Given pressures on government budgets, the Board feel that this is unlikely to change and we cannot sustain trading from this store against a backdrop of declining demand in Douglas, poor neighbourhood standards, dramatically shifting industry trends and the planned disruption to the Promenade."