Second half goals from substitute Ryan Gilligan and Northern Ireland international striker Andy Kirk secured the points for the home side at the Sixfields Stadium.
And having seen his side bag seven goals in their last two matches, the Rovers boss was understandably disappointed with the way his side failed to make it three successive wins.
"We're very disappointed," admitted O'Driscoll. "We've had two great performances, looked like we were on the way, but this is a bit of a kick in the teeth again.
"To go a goal down was something out of the blue, but something which happens in football. But I thought we responded really well, showed great attitude, but just couldn't force the ball into the net.
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"You're disappointed to concede any goal, whether it's flying into the top corner or they're scrappy goals from two yards out.
"But we've created chances all night. We've created chances and their goalkeeper was man-of-the-match."
Northampton shot-stopper Mark Bunn produced two superb saves in the space of 11 second half minutes to first deny Mark McCammon, then striker partner James Hayter who looked destined to score with a fierce right-volley from close range.
But with Rovers forced to chase the game after Gilligan's 50th minute opener, O'Driscoll's battling charges were caught on the counter-attack and Kirk won it for the home side when he fired home Jason Crowe's scuffed shot. "Mark McCammon had a great chance and some of our attacking play was really good. We opened them up and they defended for their lives, but you're always liable to get done on the break," added O'Driscoll.
"We stuck two more forwards on, but we lost our discipline a little bit and began to open up. It's ok to gamble, but we've got do better at not leaving holes.
"I'm disappointed we lost. We can still chase games without leaving holes everywhere, so we've got to work better at that.
"But you can't fault the players for wanting to go on and win the game, but we've got to do it in a more structured way."
Midfielder Wilson could be sidelined after a late challenge left him with a "quite sore" ankle injury, while McCammon pulled up with cramp late in the action.