Fat Face in Orchard Square is set to close on April 1, The Star understands.
And fashion shop Blue Banana is set to move into the adjacent unit, former shoe shop Schuh, in the new year to make way for flats.
Fashion store Fat Face, which has been in Orchard Square for several years, will be the latest of a string of retailers to leave the city centre. It is understood its shop on Ecclesall Road will remain open.
Orchard Square has several other food and drink outlets including a large Costa and Macpot, a macaroni and cheese restaurant, upstairs on Orchard Terrace.
Commercial agent Paul Lancaster, who has boards above the three shops, was contacted for comment.