O'Driscoll was concussed during Saturday's 13-13 draw with France, placing his participation at the Stadio Olimpico this weekend in doubt.
It could potentially be the 34-year-old centre's last Six Nations match as his contracts with Ireland and Leinster are set to expire this summer.
O'Driscoll's second centre partner of the championship, Luke Marshall, could also be missing from the team announced by head coach Declan Kidney because of concussion.
A third doubt is second row Donnacha Ryan, who is nursing a shoulder injury, with Donncha O'Callaghan on standby to replace him.
There is better news over Jonathan Sexton with the Leinster fly-half making a full recovery from the hamstring injury that forced him to miss the defeat to Scotland and draw with France.
Paddy Jackson, who has deputised in his absence, will drop to the bench with Sexton restored to the number 10 jersey.
Also back is Ulster wing Craig Gilroy, who will replace Fergus McFadden on the right wing having overcome a groin strain.
"I had been afraid I would miss the game altogether. But I worked hard over the last week and a half and did a lot of rehab and a lot of work with the physios," Gilroy said.
"It was just a wee niggle that got worse, but the time I've had off my feet recently has been a massive help and I'm buzzing now.
"I'm ready to get back playing. I'd love to be involved at the weekend."