The visitors ran out winners in the second league Manchester derby of the season thanks to goals from Bruno Fernandes and Luke Shaw, ending City's remarkable run of 21 straight wins.
Pep Guardiola's side dominated the derby in large parts but were unable to convert chances and break down a resilient United defence.
Reflecting on what was our first loss in 29 games, De Bruyne said City's relentless mentality was still there but admitted our usual sharpness in front of goal was lacking.
"The mentality was still the same from us but we just couldn't get the ball in," the Belgian admitted.
"Then we played pretty good but we didn't score and that made a difference and made a mistake with the pressing for the second goal."
The visitors were gifted the perfect start after Gabriel Jesus fouled Anthony Martial in the penalty area, allowing Fernandes to open the scoring from the spot inside two minutes.
Despite the early blow, De Bruyne feels he and his teammates could still have got themselves back into the game.
"It's not the best to be behind one minute into the game but then you still have the rest of the 90 minutes.
"I don't think we started well. We knew it would be hard from then and we played into their hands.
"We needed 15 minutes to settle. I think we then played well but we didn't score."
The defeat to United is City's first loss since November and ends a club joint-record of 28 games unbeaten, and with the loss coming against our local rivals it makes it that little bit tougher for the Belgian.
"Obviously it's not nice to lose the derby but it happens. Its never nice to lose but sometimes it can be necessary.
"We overcame some bad spells today but we have to learn from this as a group."
Guardiola's side will look to put the derby disappointment behind them, as we return to action in midweek against Southampton in the Premier League, and De Bruyne sees this as a big opportunity to bounce back.
"We move on, Wednesday is a new game and we will focus on that. We have confidence that in the next game we will put the [missed] chances in," he added.