Captain Rory Best, full-back Rob Kearney and back-row Dan Leavy are all facing a race against time to participate in Ireland's November internationals.
Ulster hooker Best tore his hamstring in training last Thursday and missed the province's thrilling 27-20 Pro14 win against the Scarlets.
Best will miss the first two Champions Cup pool games against Wasps and La Rochelle in October and could struggle to recover sufficiently in time to figure for his country against South Africa, Argentina and Fiji.
Seventy-nine time cap-winner Kearney was withdrawn at half time against Cardiff Blues with a hamstring injury nine days ago and has now been ruled out for between six to eight weeks.
Leavy was also replaced during the second half of the same game with an ankle injury. Leavy had surgery on his ankle last week and has also been ruled out for up to two months.
They will both be absent for Leinster's Champions Cup openers against Montpellier and Glasgow.
Best's absence would also reignite debate about the Irish captaincy.
The 35-year-old retained the role with Ulster this season and skippered the Lions’ midweek side in New Zealand.
Joe Schmidt first made him his captain ahead of the 2016 Six Nations. Leinster flanker Rhys Ruddock led the side that toured the USA and Japan in the summer with Best on Lions duty.
November series fixtures
Ireland v South Africa, Aviva Stadium, Saturday, 11 November 11, 5.30pm
Ireland vs Fiji, Aviva Stadium, Saturday, 18 November, 5.30pm
Ireland v Argentina, Aviva Stadium, Saturday, 25 November, 5.30pm