Will Addison will miss several months after suffering a setback in his rehabilitation from a back injury.
The centre-cum-full-back has required another surgery on a long-running problem with his back.
Meanwhile, Tom O'Toole's been ruled out for "several weeks" with an ankle injury suffered in the Guinness PRO14 final.
Addison sustained the injury in January of 2019, during Ireland's Six Nations training camp in Portugal. It saw him ruled out of last year's World Cup as a result.
He originally went under the knife in April 2019 to rectify the issue.
"Backs are complicated issues", Ulster coach Dan McFarland said in August when asked about Addison's progress.
"It’s really frustrating, for no one more than Will. I feel for him.
"It has been niggling at him for a while. He has a history of back [problems] over the last while and he has dealt with it really well.
"The help that he is getting from the medical performance team and the IRFU medical performance team who are involved in this intimately, has been excellent.
"We will see where it takes us. But we are positive at the moment because he is making progress."
That progress has reached a juddering halt, and no time frame has been placed on his recovery.
Stuart McCloskey and Billy Burns are both unavailable for this week's Guinness PRO14 opener with Benetton. They suffered respective elbow and calf injuries in the Heineken Champions Cup quarter-final defeat to Toulouse.
It was confirmed on Tuesday that 600 Ulster fans will be allowed inside Kingspan Stadium for Friday's game against their Italian opponents.
Kyle McCall sustained a concussion in the recent Ulster ‘A’ Inter-pro fixture against Leinster and will follow Return to Play protocols.
Ethan McIlroy (ankle) was also injured during this match and, as a result, is unavailable for selection this week.