Mr. Pirlo sustained a calf strain Friday. The team doctor told reporters that Pirlo will miss Italy’s June 14 opener against Paraguay. And his availability for Italy's second match, against Slovakia, remains in question.
But Pirlo is far from alone.
Some of the world's biggest stars will miss early games due to injuries and others have just recently been knocked out of the Cup altogether. And their absence could have a huge effect on some of the top-ranked teams in the tournament, which begins Friday in South Africa.
To date, every World Cup held outside Europe has been won by a South American team. Will that pattern continue? A healthy Argentina team and nearly healthy Brazil team help their prospects as the best European teams are now hampered with injuries.
Here's a rundown of key players who may miss the World Cup – or at least the opening matches.
ITALY: Pirlo, winner of the Bronze Ball in the 2006 World Cup, was integral to Italy’s championship at that tournament in Germany. But his potential absence isn't the team's only concern. Midfielders Mauro Camoranesi, Claudio Marchisio, and Angelo Palombo are facing injuries, according to Sky Sports.
IVORY COAST: Didier Drogba broke his forearm Friday and underwent surgery Saturday. He is one of the world's top strikers and highest paid players (as a member of English Premier League champions, Chelsea). Mr. Drogba hopes to return in time for the June 15 opener against Portugal.
ENGLAND: The Brits face two major losses in key defender Rio Ferdinand and superstar David Beckham – both out of the World Cup because of injury. Striker Wayne Rooney, considered one of the best players in the world, is still recovering from an injured ankle. (Correction: The original version of this article incorrectly stated that Mr. Rooney is the English team's new captain.)
SPAIN: Top striker Fernando Torres, midfielder Cesc Fàbregas, and Andrés Iniesta have all battled injuries this season. But Mr. Torres, while initially expected to miss the World Cup, has quickly recovered from an ankle injury and is now expected to play.
GERMANY: Captain and star midfielder Michael Ballack will miss next month's World Cup 2010 due to an ankle injury.
GHANA: "The Bison" Michael Essien is out with a knee injury.
Is there a common thread to the injuries? Most of the players listed play in the English Premier League. The New York Times argues that the League’s rough nature and crowded schedule have contributed to the injuries:
Some of the world’s most accomplished and explosive players are limping into the World Cup, if they have made it here at all, and few are as bruised and battered as the stars of the English Premier League, where the physical nature of play is particularly unforgiving.
“England is probably one of the roughest leagues in the world,” said United States goalkeeper Marcus Hahnemann, who plays for Wolverhampton. “A foul in England is a foul. In another country, they’re wondering if it’s a red card or a yellow card.”
… Injuries are part of the game in any league. But when players get minor injuries, and fixture congestion reduces the time they have to heal, those injuries can worsen. And the situation seems most acute in the Premier League.