Ronald Koeman revealed Jeremie Frimpong's substitution was due to an injury in a "blow" to the Netherlands in their 1-1 draw with Ecuador.
Willian Pacho's third-minute own goal had given Netherlands the lead, but Denzel Dumfries was shown a straight red card just nine minutes later.
Enner Valencia then equalised from the penalty spot and Koeman's side held on for a 1-1 draw, though they were forced to take off half-time substitute Frimpong.
The Liverpool right-back entered the fray at the start of the second half, but 14 minutes later, he made his way back off the field.
While Koeman did not confirm what type of injury Frimpong had suffered, he has already been sidelined three times for Arne Slot's side by muscle injuries this term.
"That was a blow, we had to substitute him," Koeman told NOS of Frimpong's injury.
Koeman had already raised frustrations with the fitness of his squad, with the likes of Jurrien Timber, Frenkie de Jong and Memphis Depay all missing due to various issues.
"I saw good things again. Throughout the entire international period, in fact," Koeman added. "The way the group interacted with each other was very good.
"It is not even that I have a definitive idea in my head which 26 they will be. But there are quite a few I have clarity on. There are also points of discussion. And we have to wait and see regarding the players' fitness.
"Only eight weeks left, but above all, I hope that everyone stays fit. And that I have to make difficult choices. That is what I am the national coach for.
"We are in a good position with Oranje, I do think so. However, we need to be fit and complete; we know that.
"We were missing three starting players with some extras: Jurrien Timber, Frenkie de Jong, and Memphis Depay. The overall fitness of a number of guys could also be a bit better. I think we are in a good position, but you can't be certain."
While the Netherlands' attacking play suffered due to the early red card (two shots in total), they defended resolutely as Ecuador peppered 17 efforts towards goals, though only three were on target.
"You want to finish with eleven against eleven," Koeman said of the performance.
"But on the other hand, it was a scenario you might also encounter at a major tournament. Then you have to go for the result together. I thought that went very well throughout the entire second half."