Fitzgerald ruled out of Six Nations
The Leinster player sustained the injury during Ireland's training session at the Aviva Stadium on Friday, and could be out of action for two months.
The 28-year-old impressed off the bench in Ireland's 20-43 World Cup quarterfinal defeat to Argentina, and would have been hoping to force his way into boss Joe Schmidt's starting line-up.
"Luke Fitzgerald has been ruled out of the Six Nations with a medial ligament injury to his knee," said Ireland's team manager Mick Kearney.
"He is expected to be out of action for six to eight weeks and at this stage no replacement has been called in.
"He was just doing a tackling drill at the Aviva on Friday, his foot got caught in the grass.
"It was fairly innocuous but very unfortunate and he's very unlucky to be out of the Six Nations."
Ireland are already without Ulster wing Tommy Bowe, still a long-term casualty with knee trouble.
Head coach Joe Schmidt can still call on Andrew Trimble, Dave Kearney and Keith Earls for the wing, with Simon Zebo able to feature out wide or at fullback.
Ireland kick off their Six Nations campaign at home against Wales on Sunday, before travelling to France the following weekend.
The Irish are then away to England on February 27 before rounding off the tournament with two home games against Italy and Scotland on March 12 and 19 respectively.
Agence France-Presse
