Keith Earls has been ruled out of Ireland's autumn internationals after undergoing surgery on his right knee.
The Munster winger is expected to be sidelined for three to four months.
Earls sustained an injury to his patellar tendon over the summer and has been unable to recover through conservative rehabilitation.
Lock Donnacha Ryan will definitely miss the November series, while Jonny Sexton, Cian Healy and Peter O'Mahony are all injury concerns for Ireland.
Ryan requires toe surgery and Leinster prop Healy faces a significant lay-off after suffering a hamstring injury in training.
O'Mahony is back in training after undergoing reconstructive surgery on both shoulders last spring, while Sexton is struggling to overcome a broken jaw sustained while playing for Racing Metro.
Earls met with a specialist on Monday, who confirmed that he required surgery.
He is also set to miss Munster's pool matches in the European Champions Cup, as well as several Pro12 fixtures.
After facing South Africa on 8 November, Ireland take on Georgia and Australia over the following two weekends.