The Dutchman was presented with his third start in four games after returning from an ankle problem earlier this month.
Barcelona took the lead through Andreas Christensen, before Vinicius Junior dispatched his spot kick to pull his side level.
As the first half drifted towards its conclusion, Barcelona were dealt a significant blow when De Jong picked up a worrying injury following a challenge by Federico Valverde.
De Jong was in agony and visibly upset by the apparent ankle injury, which was tended to by the Barcelona medical staff before a stretcher was called.
De Jong sustains serious-looking injuryThe crowd inside the Santiago Bernabeu applauded De Jong as he was stretchered off and replaced by Pedri on the stroke of half time.
In De Jong's absence, Barcelona retook the lead through Fermin Lopez, before Real Madrid's Lucas Vazquez found the net to set up a grandstand finish.
Jude Bellingham ultimately proved to be Real Madrid's hero once again, scoring a stoppage-time winner against Barcelona for the second time this season to move Los Blancos 11 points clear at the top of the table with just six matches left to play.
Outgoing Barcelona boss Xavi will anxiously wait to find out whether De Jong will be available for the closing stages of the campaign.
De Jong doubtful for Euro 2024Former Barcelona manager and current Netherlands head coach Ronald Koeman will also be hoping that De Jong's injury is not a serious one, with just under two months to go until the start of Euro 2024.
Koeman has already had to cope without the midfielder for the Netherlands' last six internationals due to ankle issues.
Despite
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