The retailer, which also owns the Fresh & Wild chain, plans to open its 125,000 square feet store on the site of the former Barkers department store on London's Kensington High Street next year.
Whole Foods Market has yet to announce the opening date or disclose details about the store, except to say that it may contain a yoga studio. It plans to open at least 40 further outlets across the UK before expanding into mainland Europe.
The retailer, which is approaching agencies directly, refused to comment on the pitch or expand on which consumers it would target.
The organic market in the UK is worth about £1.6bn and is growing at about 30% a year, according to campaigning environmental charity the Soil Association. This compares with an average yearly growth of about 3% in the UK food and drinks market as a whole. Supermarkets account for £1.2bn of all UK organic food sales. Globally, the organic food and drink market is now worth almost £17bn.
Whole Foods Market acquired organic food and natural remedies retailer Fresh & Wild in January 2004. It now operates seven Fresh & Wild UK stores, including branches in London's Soho and Notting Hill as well as Bristol.
Founded in 1980 in Austin, Texas, Whole Foods Market now has more than 180 stores across the US. In July, the company announced its fourth-quarter sales had increased by 18% year on year to $1.3bn (£684m). However, the growth was less than forecast and resulted in an 11.8% drop in its share value earlier this month.
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