SE1 could lose one of its two remaining crown Post Office branches under plans to seek "potential franchise partners" for the Blackfriars Road office.
Last month the Post Office named Blackfriars Road as one of 20 branches where the company "will advertise for suitable potential franchise partners and local businesses that have the potential to open new branches in the area".
"Some crown branches are continuing to grow profitably but others cannot do so due factors such rising rents, changing town centres or other local circumstances," said Roger Gale, general manager of the Post Office crown network.
"We need to adapt our approach so we can secure access to our services in these areas for the long term.
"By working with partners to locate Post Office branches with other retail businesses we can keep branches at the heart of communities, providing services for our customers cost-effectively and often with the benefit of longer opening hours."
The Post Office says the proposal for Blackfriars Road will be subject to public consultation.
Elsewhere in Southwark, the Walworth Road and Rye Lane Post Offices are also under threat.
The Communication Workers Union is currently balloting its members on potential strike action at crown Post Offices across the UK.
Dave Ward, general secretary of the CWU, said: "The Post Office as we know it is on the brink of extinction.
"It is clear that the board's plan is one of closure, redundancy and cost cutting on an epic scale which will permanently undermine this great British institution.
"We are repeating our call for the board to resign with immediate effect and be replaced with people who are actually interested in delivering jobs and services through this iconic brand."