Conor Murray has been ruled out of Ireland's autumn Test against New Zealand on Saturday.
The British and Irish Lions scrum-half has not played since damaging his neck on Ireland's summer tour to Australia in June, and was omitted from the 42-man autumn squad.
Ireland head coach Joe Schmidt had insisted after Saturday's 28-17 win over Argentina that Murray was still in the running for a surprise return to take on the All Blacks.
Murray has now been ruled out however, with Ireland also missing potent centre Robbie Henshaw, who has hamstring trouble.
"Conor Murray is accelerating through his recovery but will not join the squad during the Guinness Series window," the Irish Rugby Football Union (IRFU) confirmed in a statement.
"Robbie Henshaw's hamstring issue will rule him out of the remainder of the series.
"After the opening game of the 2018 Guinness Series at the Aviva Stadium on Saturday evening a couple of players will be managed in training today following a physical encounter against Argentina but all are expected to train fully on Tuesday and Thursday."
Leinster and Lions centre Henshaw pulled out of Saturday's Argentina match in the warm-up, with Ireland initially hopeful he would be ready to take on New Zealand.
But now he will miss the remaining two autumn matches, leaving a sizeable hole in Ireland's line-up.
Head coach Schmidt will hope Bundee Aki shakes off the minor ankle issue he picked up against the Pumas, though he was reported to be walking around unimpeded in the immediate aftermath of Saturday's Dublin victory.
Garry Ringrose is expected to be fit to face the All Blacks after a sore hip, and his availability would hand Schmidt a significant boost.
Ireland will also be without Sean O'Brien to take on the back-to-back world champions New Zealand, after the Leinster flanker broke his arm against Argentina.
Hamstring injury sidelines Lee
Samson Lee has been released from Wales' autumn Tests squad due to a hamstring injury,
The Welsh Rugby Union said that prop Lee, who was not fit for Wales' opening November games against Scotland and Australia, has been released back to the Scarlets for further treatment.
The WRU also confirmed that full-back Leigh Halfpenny suffered concussion during Wales' 9-6 victory over Australia two days ago and is currently undergoing relevant protocols.
Regarding 38 times-capped Lee, the WRU said: "It is envisaged the injury would prevent him from taking any part in Wales' remaining two autumn fixtures, so he has been released back to the Scarlets for further treatment."
Halfpenny, meanwhile, was on the receiving end of a challenge by Wallabies centre Samu Kerevi that forced him off seven minutes from time, but it went unpunished by referee Ben O'Keeffe.
Wales head coach Warren Gatland is expected to make wholesale changes for next Saturday's Principality Stadium clash against Tonga, which Halfpenny would probably have been rested for anyway, but he will be key to Welsh hopes of beating South Africa in 12 days' time.
