The 47-year-old director, who picked up the Outstanding British Film prize at the BAFTAs last month, is too busy with his theatre commitments to helm the 24th chapter of the Daniel Craig-fronted spy franchise.
Mendes has regretfully decided to pass up producers Michael G Wilson and Barbara Broccoli's "generous" offer, reported Empire magazine.
"It has been a very difficult decision not to accept Michael and Barbara's very generous offer to direct the next Bond movie," Mendes said.
"Directing 'Skyfall' was one of the best experiences of my professional life, but I have theatre and other commitments, including productions of Charlie And The Chocolate Factory and King Lear, that need my complete focus over the next year and beyond," he added.
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However, the filmmaker doesn't want to leave the Bond family for good and hopes to be involved in secret agent 007's adventures in the future.
"I feel very honoured to have been part of the Bond family and very much hope I have a chance to work with them again sometime in the future," he added.