England captain Rio Ferdinand and Ivory Coast skipper Didier Drogba became the latest high-profile World Cup injury victims on Friday.
The Manchester United defender Ferdinand, 31, suffered a knee injury towards the end of training on Friday at their South African base camp in Rustenburg.
He was taken to hospital where a scan revealed he won't be able to play at the World Cup, according to British media reports.
Drogba broke his right arm in a clash with Japan defender Marcus Tulio Tanaka during a tune-up match in Sion, Switzerland, which Ivory Coast won 2-0.
The injuries came on the same day as the official squad lists were released by the ruling body FIFA. Both teams are allowed to name a replacement.
Ivory Coast team officials are yet to fully rule Drogba out of the World Cup, but he is unlikely to recover in time for the tournament which starts next week Friday.
Drogba, 32, is the third major player from English champions Chelsea on the sidelines, joining Germany captain Michael Ballack and Ghana midfield star Michael Essien.
Essien failed to recover in time from a knee injury while Ballack's dream ended in a tackle from Portsmouth defender Kevin-Prince Boateng in the FA Cup final on May 16.
Ballack was the biggest blow for a hard-hit Germany team which also misses first-choice goalkeeper Rene Adler as well as midfielders Simon Rolfes, Heiko Westermann and Christian Traesch.
England had an injury setback ahead of Ferdinand's agony, as former captain David Beckham's chances of making the squad for the June 11-July 11 tournament ended in a ruptured Achilles tendon while playing for AC Milan in March.
Apart from the injured, other major players didn't make the cut for other reasons.
Dutch striker Ruud van Nistelrooy failed to get a recall after retiring from Oranje in 2008 and Brazil coach Carlos Dunga overlooked the prominent trio of Ronaldo, Ronaldinho and Adriano.
There was no place on the France squad for striker Karim Benzema and Patrick Vieira, and veterans Luca Toni and Francesco Totti were also not good enough to represent title holders Italy.
There were raised eyebrows in the host country of South Africa when coach Carlos Alberto Parreira overlooked the nation's best scorer Benni McCarthy in his final 23-player list.
Others like Sweden striker Zlatan Ibrahimoic or Russia winger Andrei Arshavin didn't even get that close, for the simple reason that their teams failed to qualify.