Mark Cavendish (HTC-Highroad) abandoned the 2011 Vuelta a Espana during the race's first mountains stage to Sierra Nevada on Tuesday.
Cavendish had been one of a number of riders that had suffered in the severe heat during Monday's stage three, dropping back with a group of 30 that finished 12 minutes and 50 seconds behind stage winner Pablo Lastras (Movistar).
Cavendish had been hoping to use the Vuelta as preparation for his bid on the road race World Championship title later in September.
Cavendish's HTC-Highroad room-mate Matt Goss was the first rider to abandon the 2011 Vuelta on Sunday after suffering from a stomach complaint.
No official explanation has so far been given for Cavendish's withdrawal.
Cavendish has already completed the Giro d'Italia in May and Tour de France in July, in which he won five stages and the points classification overall.
Vuelta a Espana 2011: Cycling Weekly's coverage index
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Climbers set to dominate in 2011 Vuelta
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Vuelta a Espana 2011: Teams, riders, start list
Vuelta a Espana 2011: Who's riding?
Vuelta a Espana 2011 team list
Vuelta a Espana 2011
: Stage reports
Stage three: Lastras solos to stage and takes red jersey
Stage two: Sutton grabs stage win to set things right for Sky
Stage one: Leopard-Trek win opening TTT to put Fuglsang in front
Vuelta a Espana 2011: Photo galleries
By Graham Watson
Stage two photo gallery
Stage one photo gallery
Vuelta a Espana 2011: TV guide
Vuelta a Espana 2011: ITV4 TV schedule
Vuelta a Espana 2011: British Eurosport TV schedule
ITV to show 2011 Vuelta
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