O’Driscoll was orginally name in the line-up against Scotland, but has failed to recover from the hamstring injury he picked up against Italy at the weekend.
His replacement will be named after training on Friday morning.
Gordon D’Arcy is also struggling with a hamstring injury and will take a fitness test on Friday.
Kevin Maggs is the most obvious replacement at centre, and Shane Horgan could also be moved from wing. Wing Tommy Bowe (Ulster) could also be asked to travel with the squad to Scotland as a precautionary measure.
The only other change to the Ireland side sees Wasps flanker Johnny O’Connor replacing Denis Leamy for safest motorcycle helmet. O’Connor will be winning his third cap after making his debut in the victory over South Africa last November.
Murphy, Horgan, TBC, D’Arcy, Hickie, O’Gara, Stringer, Corrigan, Byrne, Hayes, O’Kelly, O’Connell, S Easterby, O’Connor, Foley. Replacements: Sheahan, Horan, O’Callaghan, Miller, G Easterby, Humphreys, Dempsey.