Burton were so superior in the first half an hour they might have been four up.
With on-loan Wolves playmaker Zeli Ismail on fire, and Jimmy Phillips lending excellent support, Burton threatened to score every time they attacked.
Dominic Knowles fired them in front from Ismail's pass in the 10th minute, Ismail scored a thumping second on 26 minutes and then Phillips was brought down for a penalty two minutes later, only for Billy Kee's spot kick to be well saved by keeper Ryan Clarke.
But Oxford's automatic promotion hopes are fading fast. Having lost to third-placed Rochdale last week, this was another damaging defeat to a promotion rival, and the play-offs are now looking more realistic for them than automatic promotion.
Lewis said: "We could easily have got a draw or even won it in the end.
"I was really pleased with the second-half performance but we gave ourselves too much to do.
"We're not on a great run but when we got back into the dressing room and see the other results, you can see that a lot of teams in and around us are not on great runs at the moment either.
"Some of our players are just not performing well at the moment. That happens in a season.
"We made mistakes in the first half and gave ourselves a mountain to climb.
"To draw positives, we created quite a lot of chances in the second half.
"We just need to get back to defending how we did earlier in the season."
To add to Oxford's woes, they had star striker Dave Kitson limp off after half an hour.
"Kitson came off with the same hamstring injury he had earlier this season, so he will probably be out for a few weeks, which is a blow," Lewis admitted.
"But we've got David Connolly, and he was excellent for us in the second half."