More than 20 jobs are to go at Santander's banking centre in Douglas.
The company says it's reducing total staff numbers from 53 to 32 in the year ahead, due to changes in its Island business.
Last year the firm's office in Prospect Hill moved from being a wholly owned subsidiary of Santander UK to a branch in its own right - when it was rebranded to Santander.
A statement from the firm says fewer staff will be needed after the introduction of a new IT platform for both personal and business customers.
Staff will be offered redeployment or relocation but redundancies are not ruled out.
Managing director of Santander Isle of Man John Pearson said: "Santander is committed to having a sustainable retail and wealth focussed business on the Isle of Man and is committed to having a presence here."
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