Goalscoring debutant Stuart Dallas made his full Town debut at the Kassam Stadium after scoring within 15 minutes of coming on as a substitute at AFC Wimbledon last week.
The Northern Ireland international, on loan from Brentford, had inspired the Cobblers to their first away win of the season.
Aidy Boothroyd named the following side for the trip to the Kassam Stadium: Duke, Amankwaah, Reid, Doumbe, Tozer, Collins, Dallas, Deegan, Carter, Morris, O'Donovan.
Having fought a determined rearguard action in the opening 45 minutes, Town were undone on the stroke of half-time after good work from Kitson and Whing to set up James Constable for the opening goal.
If that was not bad enough Constable then won a penalty in stoppage time which Rose converted to completely alter the nature of Aidy Boothroyd's half-time team talk.
Ivan Toney came on as half-time substitute for the Cobblers and Aidy Boothroyd also threw JJ Hooper into the fray but to little avail as Oxford closed the game out.
6,177 watched the action with a healthy contingent of Northampton supporters left to reflect on an unchanged league position of 23rd.
Reaction: Aidy Boothroyd lamented 'five minutes of madness' which cost his side any chance of a result in the game.
"We just knocked off when Constable scored.
"I don't think it was a penalty after that, but he shouldn't have got in there in the first place, and we were responsible for that."