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The veteran centre, who missed the November programme through injury, returned to action with a superb display in Ireland's opening 30-22 win over defending Grand Slam champions Wales last week, creating one try, scoring another and producing several crunching tackles in defence.
Now he is relishing another crack at England.
"They're great occasions, largely because invariably England are one of the best sides in the world," said O'Driscoll, who hinted before the Wales match this could be his last Six Nations.
"You have to bring your 'A' game. It's England in Dublin and that's an exciting prospect no matter how many times you've had it."
O'Driscoll, 34, does not expect to play at the 2015 World Cup in England and has said he understands why Ireland coach Declan Kidney has entrusted the captaincy to back-row forward Jamie Heaslip.
But he remains a leader all the same and Sunday should see O'Driscoll and Gordon D'Arcy, provided he recovers from a dead leg, extend their world record centre partnership to 49 Tests.
By contrast, England's Billy Twelvetrees and Brad Barritt will be playing just their second match together if coach Stuart Lancaster sticks with the midfield pairing that starred in the 38-18 win over Scotland at Twickenham.
The talented Twelvetress marked his Test debut with a well-taken try while Barritt, one of the heroes of England's victory over world champions New Zealand in December, anchored the defence.
However, one of the duo could miss out if Lancaster recalls the fit-again Manu Tuilagi, who scored one and created two of England's three tries against the All Blacks.
"There are selection decisions across the field and that's one of them. Billy played well and Brad's contribution as always was positive," Lancaster said.
"But Manu brings a unique set of skills and attributes to the game and the team, as we saw in his performance against the All Blacks."
D'Arcy, however, was relishing the challenge.
"Manu's a unique player and a powerhouse. His ability to get over the gainline is phenomenal," he said.
"But Brian and I love defending. We've always been up against really good players over the years and we've always held our own."
Twelvetrees certainly made his presence felt against Scotland but, if selected, is unlikely to have things all his own way in Dublin, where England have not won a Championship match since they last completed a Grand Slam months before their 2003 World Cup triumph.
Indeed such has been the turnaround since Lancaster first took charge last year that England -- who did win a 2011 World Cup warm-up match in Dublin -- are unlikely to have many survivors from the team that saw a Grand Slam dashed at Lansdowne Road two years ago.
One of the likely exceptions when Lancaster names his team on Friday (as will Kidney) is Chris Ashton.
For the wing, who scored his 17th try in 30 Tests last week, the memory of that 24-8 thrashing under then England boss Martin Johnson remains vivid.
"In the changing room it felt quite tense and isolated. The environment now and the culture of the team have altered because of what Stuart Lancaster has done," Ashton said.
Yet for all the pace and talent behind both scrums, the breakdown battle between back-rows led by Heaslip and England captain Chris Robshaw is set to determine the outcome of Sunday's match.
However, both sides may have to make injury-enforced changes in this key area, with Ireland's Peter O'Mahony trying to overcome a head knock and England No 8 Ben Morgan set to give way to James Haskell because of an ankle problem.