The Argentine believes that his side played admirably against its cross-city rival but regrets the failure to take its chances in front of goal.
Radamel Falcao gave los Rojiblancos an early lead but an own goal from Juanfran and an Angel Di Maria winner ensured that it was the visiting side that took all three points with a 2-1 win.
Speaking to journalists after the game, Simeone praised the performance of his team but confessed that the profligacy in front of goal had frustrated him.
"The merits do matter, but the goals are what count," the 42-year-old Argentine said. "They were more convincing in front of goal. We've had the match we needed to have, but we went without the result. It was a missed opportunity.
"The match started very well, but then they got their goal not long after ours. Regarding the performance, on the face of the way of playing and intention of winning, that was always there. For the first 30 minutes we played in the half of our rivals, but this is the grand thing in football, the ones who get the goals win."
The defeat leaves los Colchoneros six points behind Jose Mourinho's side in La Liga, but Simeone stressed that there will be other opportunities to overcome Real Madrid, with the Copa del Rey final offering his team a chance of redemption.
"There’s another chance in a short while, two next year and another two the next," the former Argentina midfielder added. "There will always be opportunities and hopefully we can win the most important game. We have another opportunity on the 17th May [the date of the final], which certainly many feel isn't possible, which is better for us."