Mikel Arteta believes players are at risk from suffering burnout as the truncated fixture calendar gives them little time to rest and recuperate.
The Arsenal boss lost Kieran Tierney to a calf problem just hours before Thursday's Premier League stalemate with Crystal Palace.
Pablo Mari also missed out due to a similar issue, with the pair having played the entirety of the previous four matches.
Speaking after the goalless draw with Palace, full-back Hector Bellerin said players' bodies "can only cope with so much" in such a busy season.
Ahead of Monday's visit of Newcastle, Arteta echoed those sentiments and feels the injuries suffered by the likes of Tierney and Mari will become more commonplace before the end of the season.
Asked if there was a risk of burnout due to the amount of games, Arteta replied: "Yes. We have been trying to manage it.
"But the reality is that the fixtures are what they are and we didn't have a pre-season, which is why – and we've talked about it many, many times – one of the reasons we wanted the five subs.
"It was exactly that. But this is just the consequences and this will happen more and more, I think, and to more clubs."
The Premier League remains the only one of Europe's top five leagues not to reintroduce five substitutions per game to ease the load on players.
Arteta feels players are getting injured because they are being asked to play too many minutes and hinted at changes to his side for the Newcastle game.
"Yes, but when you are winning, you want to be in the team," he said when asked if more changes could be made on Monday.
"When someone is doing well then you don't want to take him out because you get asked: 'why are you taking him out?'
"The players also want to continue to play because they can't see the bigger picture but it's our responsibility to protect them.
"We could have taken a big risk with Kieran against Palace and it wasn't the right one to take because we could have exposed him big time."