Boots has confirmed it will close around 200 stores across the country in the next 18 months, most of them local pharmacies.
The retail chain said its owner, Walgreens Boots Alliance, has now approved a plan which will see primarily local pharmacy branches shut down in locations where there are other stores nearby.
It is unclear how many jobs will be affected, with Boots promising to find new roles for affected staff.
The news came a day after Boots opened a new flagship store in Covent Garden. London, creating 130 jobs.
Sebastian James, managing director of Boots UK and Ireland, said: "We believe this is the right thing to do as it means that we can invest more in staffing those stores while not reducing our 90% coverage within a 10-minute drive of a Boots.
"We do not anticipate a significant effect from this activity to colleagues as we will redeploy the overwhelming majority to neighbouring stores."
The changes are part of wide-ranging cost reduction plans by Walgreens, which on Thursday revealed its profits had been hit by declining retail sales in the US and UK.
Bosses would not confirm which locations were at risk of closure.
"We cannot confirm specific stores at this stage as we have only started the optimisation process," a spokesman said.
Boots said it was part of a wider change to their store portfolio, and not a case of the chain pulling back.
Usdaw, the union for retail workers, called for the company to enter talks and said it was 'worrying' news for employees.
National officer Daniel Adams said: "We urge the company to engage with Usdaw as the trade union for Boots retail staff to ensure that all avenues to minimise job losses are explored during this critical time.
"This issue is not confined to Boots; our high streets are in crisis and we need the Government to adopt a clear and coherent strategy for retail, to address the worries and concerns of shop workers and our members."
