The store at Unit 13, Baddeley Court, 6-16 High Street, Newport, will help to raise money for vulnerable children across the UK.
Barnardo’s is now keen to receive donations, including good-quality clothing, books, DVDs, toys, games, accessories and homeware.
Barnardo’s regional cluster manager Jason Worley said: “We are delighted to be opening our store in Newport.
"By donating goods and shopping in the store, customers will be helping to raise much-needed funds to help Barnardo’s support vulnerable and disadvantaged children and young people.”
The charity is also looking for local volunteers who can spare a few hours a week to help the staff with sorting stock and serving customers.
Anyone who would like to volunteer should call 07514 719449.
Store manager Steph Millward said: “We hope to become an important part of the local community.
"Volunteering provides valuable experience for those seeking employment, as well as a great opportunity to meet new people and make new friends. We hope the people of Newport will help us to give children a brighter future.”
The Barnardo’s shop opens on Friday, February 10, and will be open Monday to Saturday from 9am-5pm, and on Sundays from 10am to 4pm.