"With four minutes to go we still had everything to play for," said O'Driscoll, after late tries from Mike Phillips and Croft had given the Lions hope of overturning a 26-7 deficit in Durban.
"We were in the ascendancy, had ball and they were panicking bit.
"So the overriding feeling is disappointment.
"We scored three tries against the world champions - that will give us huge heart - but essentially it's a loss."
O'Driscoll has tasted defeat on his two previous tours as a Lion and he is desperate to avoid an unwanted hat-trick this time around.
The 2005 Lions skipper knows that steering clear of such an outcome will be a huge challenge but he does believe the current crop of tourists have the ability to ensure they take the three-match series to a decider by winning in Pretoria this time next week.
"We are going to have to do it the hard way," O'Driscoll told Sky Sports.
"The first Test is very important. Essentially now we have got two cup finals, with no margin for error.
"We have to have that second-half performance for 80 minutes next week. We know we've got it in us.
"We know what we're capable of doing to the South African side. I think they were worried at times in that game and hopefully we can bring that positivity and enthusiasm into the start of Saturday's game."