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The agency will close six of its 80 district offices, eliminate some 1,400 management and supervisor posts across the country, and offer early retirement opportunity to 150,000 workers.
"These actions are expected to save the Postal Service more than 100 million dollars annually," the agency said in a statement.
Battered by shrinking mail volume and rising costs, the post office lost 2.8 billion dollars last year and is headed toward larger losses this year.
Earlier this week, the agency announced that economic woes are forcing it to delay release of several new postage stamps scheduled for this year.
"The Postal Service is streamlining operations and improving efficiencies across the board in order to protect its ability to provide affordable, universal mail service," said the agency in the statement.
An independent federal agency, the U.S. Postal Service is the only delivery service that reaches every address in the nation, 149 million residences, businesses and Post Office Boxes, six days a week.
It has 34,000 retail locations and relies on the sale of postage, products and services, not tax dollars, to pay for operating expenses.