The British Heart Foundation store in Millers Walk, Fakenham is among the first 87 branches set to close permanently, with further sites still at risk.
The charity announced that the first wave will close by March 2027, following a review of its retail estate.
A total of 150 of the brand’s 640 locations will then shut across a two-year period due to rising operational costs, decreased footfall and changes to consumer habits.
British Heart Foundation chief executive, Dr Charmaine Griffiths, said: “Our shops mean so much to our colleagues, brilliant volunteers and communities across the UK.
“They are places where people come together to donate, shop and volunteer, helping to make a real difference to lives affected by cardiovascular disease.
“We know this will be a difficult time for our dedicated colleagues and volunteers in affected stores and emphasise our deep appreciation and gratitude for all they have done for BHF and the communities they serve.
“Like most retailers, we are facing an exceptionally challenging trading environment.”
Allison Swaine-Hughes, the group’s chief commercial officer, said: “Our success to date has been shaped by the dedication and contribution of our teams across the UK and this has been an incredibly difficult decision following a thorough and careful review.
“We must act now to ensure a sustainable future for BHF retail.
“Change is essential so we can continue to serve communities across the UK and raise the funds that power our lifesaving research.”
A further 63 stores could be at risk while the second wave of closures remains yet to be finalised.
Norfolk has seven shops including in Norwich, Thetford, Sheringham, Fakenham, and Great Yarmouth.
The foundation will support impacted employees throughout the closures, with opportunities for redeployment offered wherever possible.
Customers will be able to donate and shop as normal while stores remain open.