Isner held serve 69 consecutive times in the final set of his record-breaking three-day match against Nicolas Mahut which ended on Thursday, but lost his first four service games in his second-round match at the All England Club.
He called a medical timeout for treatment to his neck and shoulders after De Bakker powered to the opener 6-0 and seemed weary and off the pace throughout the encounter on Court Five.
He consulted with a trainer at most of the changes of ends, and ate bananas and bars to try and boost his energy levels but De Bakker completed a 6-0, 6-3, 6-2 rout.