Ireland captain Brian O'Driscoll will undergo surgery for a trapped nerve in his shoulder next week and is expected to be ruled out for up to six months.
The Leinster centre is now set to miss the Six Nations and the Irish province's bid to retain the Heineken Cup.
O'Driscoll struggled with a shoulder problem throughout the World Cup and missed Friday's RaboDirect PRO12 game against Munster.
In a statement on their club website, Leinster said: "It has been confirmed that Brian O'Driscoll will undergo surgery next week for a trapped nerve in his shoulder which is expected to rule the Ireland captain out for up to six months."
The loss of O'Driscoll will be a big blow for the province who have been without the 32-year-old since Ireland's Rugby World Cup quarter-final defeat by Wales in Wellington.
O'Driscoll, who earned the first of his 117 Ireland caps in 1999, will now face a race against time to return to fitness before the end of the season.
The Leinster centre is Ireland's record try scorer and in 2011 he broke the 78-year-old record set by Scotland's Ian Smith as the all-time Five/Six Nations top try scorer when he crossed for his 25th championship try against England.
O'Driscoll has been unlucky with injury, notably missing the majority of the 2005 British Lions tour to New Zealand after he suffered a dislocated shoulder following an illegal spear tackle by Tana Umaga.
Last month, the centre revealed in an interview with the Evening Herald that he wants to bow out of the game after the 2013 Lions Tour to Australia.
Leinster will begin the defence of their Heineken Cup crown against Montpellier on Saturday.