The London Bridge branch is Santander's last remaining SE1 branch.
It will close its doors for good at 4pm on Thursday 15 July.
"We know our branch network remains very important to our customers," wrote Santander's head of branch interactions Adam Bishop.
"Whilst we have made the difficult decision to close some branches, we have only done so where we know there are other facilities our customers can use and where we have another Santander branch within a few miles."
Santander says that in the second half of 2019, only 22 customers made six or more transactions at the London Bridge branch, whilst using the branch exclusively for their interactions with the bank.
The bank says that 95 per cent of customers using the London Bridge branch also use online and telephone banking.
The nearest Santander branches to remain open are in Cheapside (less than a mile away in the City of London) and the Walworth branch just over two miles away.