The talismanic duo were missed terribly during the autumn series, leaving a leadership vacuum as Ireland fell to defeats by New Zealand and Australia before victory over Romania restored some pride.
O'Driscoll has been recovering from the shoulder surgery required after he was spear-tackled by All Blacks Tana Umaga and Keven Mealamu during the first Lions Test in June.
The 26-year-old centre missed all three November internationals and made his comeback for Leinster earlier this month before crossing for two tries in Saturday's 46-22 European Cup victory over Glasgow.
O'Driscoll was exposed defensively against Glasgow but his finishing was superb, prompting Leinster coach Michael Cheika to confirm his comeback is progressing as expected.
"Brian obviously looks a bit fitter now. I'm pretty happy with the way he's going," he said.
"His comeback has come in the middle of an intense period. There's so much focus on the guy, but we must remember that he is just a footy player like everybody else."
O'Connell, out of action with a hand injury since September, made his return last month and was also in try-scoring form over the weekend, crossing twice in Munster's 46-9 demolition of Castres.
The 26-year-old's performance won rave reviews and his return will be welcomed by Ireland who lack an edge up front in his absence.
The enforced lay-offs may even have done O'Driscoll and O'Connell some good, giving them time to recharge and keeping them relatively fresh for the Six Nations.
Should the pair remain injury-free before the opener against Italy on February 4, O'Driscoll will reclaim the leadership duties with O'Connell deputising.
Llanelli flanker Simon Easterby, stand-in skipper during the autumn, will be able to concentrate on retaining the number six jersey with his place likely to come under threat over the coming weeks.
Openside David Wallace has been outstanding for Munster and is pressing hard for inclusion in the squad while Keith Gleeson, who missed most of last season with a broken leg, is also firing at number seven.
With Johnny O'Connor the incumbent openside, O'Sullivan is spoilt for choice in the position so may rejig his back row to accommodate his form players with veteran number eight Anthony Foley also back in the frame.
There is little scope for O'Sullivan to make changes in the front row so he will rely on the props who featured in the autumn, with Shane Byrne, Simon Best and Jerry Flannery in as hookers.
O'Sullivan was criticised in some quarters for refusing to select Bob Casey of London Irish or Toulouse's Trevor Brennan during November and it is possible one of them could join regular locks O'Connell, Donncha O'Callaghan and Malcolm O'Kelly in the squad.
Behind the scrum, Ireland's backs will pick themselves with Denis Hickie restored to the squad after recovering from his dislocated fibula and exciting prospect Andrew Trimble featuring once again.