O'Driscoll will undergo surgery next week to correct a trapped nerve, an injury that plagued him during the World Cup and confined him to the sidelines in last week's RaboDirect PRO12 victory over Munster.
Having been widely tipped to announce his international retirement after the World Cup, O'Driscoll's injury has further fuelled the fires, but O'Connell believes otherwise and is convinced he will return to add to his 117 caps.
"I have no doubt he will come back, absolutely no doubt," said O'Connell. "I suppose it'll be fun for people to write him off now in the papers or whatever for a few months, but I have no doubt he'll come back.
"With his mental strength and the way he is made up, I have no doubt he'll come back and he will probably have a great finish to his career because of the break.
"It'll probably do him well. Sometimes when you are rehabbing injuries all the time it doesn't do any harm to have something that rules you out for a few months so you can work on a few other things."
O'Connell believes the enforced time out could be good for O'Driscoll, who has said he hopes to be back in action for the latter stages of the Heineken Cup.
He added: "The break refreshes you and I think there is probably one or two more seasons in him, he'll probably play all the better for it.
"You can work on your speed and your strength and different things like that.
"I know when I play, I hate to play injured, you want to be 100 per cent all the time. It really rattles you when you are not. It has probably been a tough few months for him like that, but I think it is a great decision for him for his career."