They are two of a number of changes the Ireland coach will make to the team that started against Argentina in November.
O'Driscoll missed the autumn games after undergoing ankle surgery and in his absence Jamie Heaslip assumed the captaincy – an honour which the No 8 has retained for the Six Nations.
O'Brien's expected return is likely to be at the expense of Ulster's Chris Henry. The openside flanker had a very impressive autumn series and has been outstanding for Ulster in their Heineken Cup campaign, but O'Brien's thundering ball-carrying ability will be favoured on this occasion.
Kidney will also keep faith with the exciting pair of Simon Zebo and Craig Gilroy in the back three for the outing in Cardiff.
Zebo was very impressive when deployed at full-back in November, but in light of Kearney's return to fitness, the Munster flyer will move onto the left wing, with Gilroy moving to the right in place of the injured Tommy Bowe.
Meanwhile, Kearney – who would be close to the top of any French club's shopping list – has warned that Jonny Sexton's imminent departure to Racing Metro for a reported €750,000-a-year salary could be the start of an exodus of top players from Irish rugby.
So far the comparatively cash-rich IRFU has been able to fight off the advances of the French giants – and indeed their English counterparts in the Premiership – for their marquee names with lucrative central contracts, but Sexton's decision to move at the height of his career could be a defining moment.
"Jonny's shown a lot of bravery," insisted Kearney yesterday.
"If it works out really well for him in that he's enjoying life and playing good rugby while earning more money, people will see that and it will open up a whole new ball park."
IRELAND v Wales (probable) – R Kearney; C Gilroy, B O'Driscoll, G D'Arcy, S Zebo; J Sexton, C Murray; C Healy, R Best, M Ross; M McCarthy, D Ryan; P O'Mahony, S O'Brien, J Heaslip (capt).