Mothercare and the Early Learning Centre, which is located inside the store, will both be closing, on August 6.
A Mothercare spokesperson said: “We thank all our customers in the Luton area for their loyalty and support for Mothercare.
“Whilst we deeply regret that the store will close in August it is part of a larger transformation plan for our business.
“The plan will see us close a small number of our unprofitable stores across the UK whilst investing in cutting edge online shopping channels, as well as the refurbishment of some of our larger stores to make the experience even better for our customers.”
The nearest stores to Luton are in Watford, Milton Keynes and Bedford.
Kate Staniforth, The Mall’s marketing manager, said: “The Mall is committed to provide the strongest retail offer for Luton and continually in discussions with retailers to enhance the retail mix.”