Walgreens, which bought Super D's parent company, USA Drug, in July, said it's closing 76 of the stores it acquired.
Super D stores in Oxford and Starkville also are closing.
However, the Super D on South Gloster Street adjacent to North Mississippi Medical Center in Tupelo will remain open.
Also, Super D-owned pharmacies in Northeast Mississippi will stay open - Bennett Apothecary in Belmont and Yarber Drug in Corinth.
"After careful planning and market analysis, on Monday we began to notify employees of our intent to close certain stores, including a number in Tennessee, Mississippi and Arkansas," Walgreens spokesman Jim Graham said. "Our decisions about store closures are based on a number of considerations, including size of the market and proximity to other Walgreens and USA Drug stores and affiliates."
In July, Walgreens said it would buy the USA Drug chain for $438 million from Stephen L. LaFrance Holdings and members of the LaFrance family.
The deal included 144 stores operated under the USA Drug, Super D Drugs, May's Drug, Med-X and Drug Warehouse stores in Arkansas, Kansas, Mississippi, Missouri, New Jersey, Oklahoma and Tennessee.
USA Drug's total sales were $825 million in 2011.
Walgreens recorded $72.2 billion in sales in Fiscal Year 2011.
At the time of the deal, Stephen L. LaFrance said, "We chose to sell our business to Walgreens not only because it is the premier drugstore company in our industry, but also because Walgreens will continue to provide our customers with the service and products they have come to expect."
Walgreens said it would continue "in the near-term to operate under their current brand names after the transaction closes, and decisions will be made over time regarding the best, most effective way to harmonize Walgreens and the acquired brands."
It took about two months for Walgreens to decide to cut more than half of the acquired stores.
In Tupelo, the remaining Super D, at the intersection of South Gloster Street and Crossover Drive, is next to North Mississippi Medical Center. A block south, on Garfield Drive, is a Walgreens.
Walgreens has two other stores in Tupelo, at Crosstown and on Barnes Crossing Drive. Walgreens said each affected store's pharmacy customers will be notified of nearby Walgreens or USA Drug stores where prescriptions will be transferred.