The setback leaves Stoute without a runner in Europe's richest handicap. He pulled out the one-time favourite Secret Saver soon after publication of the weights.
It also means that the trainer loses the chance of a potential 1990s treble of successes in the race following the victories of Deposki in 1991 and Clerkenwell two years ago. Stoute was also successful with Shaftesbury in 1980.
The trainer said: "I would like to inform the betting public that Double Classic will not run in the Ebor. He has an infection in his near hind joint."
Double Classic was quoted as low as 8-1 and was well fancied after recording a Royal Ascot victory in the King George V Stakes. The sponsors, the Tote, were quick to produce a new market on the race with the Henry Cecil-trained Tuning their 6-1 favourite.
William Hill yesterday opened a book on this weekend's big sprint handicap, the Great St Wilfrid at Ripon, which they sponsor.
Five-day declarations for the race include last year's first and second, Tadeo and Emerging Market. However, they face stiff opposition from in- form horses in Double Oscar and Proud Native from the David Nicholls yard, while Mark Johnston's Gaelic Storm is to tackle his third consecutive Saturday handicap after chasing home Jo Mell at Ascot last week and running in Goodwood's Stewards' Cup the Saturday before.
GREAT ST WILFRID HANDICAP (Ripon, Saturday) William Hill: 10-1 Double Oscar, Gaelic Storm, Nuclear Debate, 11-1 Masha-Il, Proud Native, 12-1 Deep Space, Surveyor, 14-1 Bayleaf, Nigrasine, Sheltering Sky, 16-1 Cadeaux Cher, Friar Tuck, Perryston View, Resist The Force, Tadeo, 20-1 Double Action, Emerging Market, Fire Dome, First Maite, Indian Spark, Lago Di Varano, Levelled, Stand Tall, The Puzzler, To The Roof, 25-1 others.