O'Driscoll suffered a 'stinger' to his shoulder in the 26-22 defeat by France in Dublin last weekend and has been omitted as a precautionary measure.
"Brian picked up a knock against France. He's running around outside, but it was prudent to us not to put him into a contact situation on Saturday," said coach Declan Kidney.
"He has made good progress, especially over the last 24 hours.
"With the game coming this week and a full tournament coming up, it just wasn't prudent to put him in the mix.
"I don't have the actual medical term for the injury. He gets stingers around this area (pointing to his shoulder).
"Sometimes you just need to rest it up and get them out of the system."
Ireland's preparations for the World Cup have also been hit by the loss of O'Brien, their most consistent performer since the start of the RBS 6 Nations.
The European player of the year sustained a knee problem midway through the second half against Les Bleus, but Kidney is unconcerned by his fitness.
"Sean will be fine, it wasn't prudent to include him this weekend," said Kidney.
"But as you can see he's in training already and he'll work his way back in.
"If he is injured and he is scoring tries at the end of the game we'll take that wouldn't we."
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