Cancellara came unseated in a huge crash within the first hour of E3 and abandoned the race shortly afterwards.
The Swiss rider, who nows joins fellow Classics specialist Tom Boonen on the sidelines, went down on the Haaghoek in a group containing some of the pre-race favourites, including Milan-San Remo winner John Degenkolb and the winner of the 2014 Tour de France's cobbled stage, Lars Boom.
A picture from Sporza's cycling reporter Renaat Schotte showed Cancellara, a three-time winner in Harelbeke, back on his bike but clearly in pain from his left wrist and with scrapes down his left side.
The injury is a huge blow to both Cancellara and Trek Factory Racing's hopes of success in the Classics this season, with the Swiss explaining before the race how E3 is a good indicator of your form before next week's Monuments.
"It seems that a water bottle fell on the cobbles and caused it," Trek Factory Racing team sports director, Dirk Demol told Sporza TV.
He hit his wrist and the lower part of his back. He couldn't stay on the pedals anymore. He wasn't looking good at all."
The crash led to a number of other abandonments, with Sebastian Langeveld (Cannondale-Garmin), Niccolo Bonifazio (Lampre-Merida) and Robert Wagner (LottoNL-Jumbo) taken to hospital.
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