The Post Office is planning to close and franchise 37 Crown offices, with, the union says, the loss of 300 jobs and 127 specialist roles.
The Post Office said the changes would help to keep branches where customers wanted and needed them to be.
But the Communication Workers' Union (CWU) said the move was "evidence that the Post Office is in crisis".
The union added that the number of post office jobs lost since the beginning of last year was 2,000.
The CWU held a five-day strike before Christmas at Crown post offices in a dispute partly about branch closures. The union is also concerned about job losses and pension provision.
Crown post offices are the larger branches usually found on High Streets.
In a statement, the Post Office said: "With consumer habits changing, and the high cost of maintaining premises in prime high street locations, franchising helps us to keep services where our customers want and need them."
It said it would take time to identify the right partners over the coming months and all proposals would be subject to local consultation. It promised to keep staff "fully informed".
CWU general secretary Dave Ward said: "The latest round of closures is further evidence that the Post Office is in crisis and that the board of the company, backed by the government, is simply pursuing a strategy of slash and burn.
"Today's announcement comes less than three weeks after the closure of a major government consultation on the future of the Post Office and sticks two fingers up to everyone who took part in this."
The union said that 75,000 postcards had been sent by members of the public to the government calling for an end to the closure and franchise programme of the Post Office.
It added that the Post Office network has been reduced by more than 50% over the past 30 years.
In April 2016, the Post Office announced plans to transfer up to 61 branches into WH Smith stores over the following year.
It said the move was part of a 10-year plan to cut costs and save cash, and would act as a way of "safeguarding the future of the network".