Manager Aidy Boothroyd conceded Northampton were beaten by the better side as Oxford ran out 2-1 winners in Saturday's League Two clash.
James Constable put the hosts ahead at the Kassam Stadium and after Clive Platt climbed off the bench to level, fellow substitute Jon-Paul Pittman hit the winner.
Clarke Carlisle saw red late on for the Cobblers as he picked up a second yellow.
Boothroyd said: "We're disappointed with the result but I've got to give credit to the opposition as they came at us strongly.
"I've also got to give my players for the way they came back."
"We've been on a good run ourselves, so this is a bit of a reality check for us."