It helps to bench your best players from time to time. You will see that the substitutes will perform very well too, usually 1 or 2 matches.
Personally I have an wide selection most of the time, complete substitutes and reserves. I use them to spare my best players , in matches in which I for example overclass my oponent. This also allows me to give the subsitutes playing minutes, which then get more skill points or at least improvement. This way,I prevent my best players to get fatigued, also save them from injuries and cards
It has happened very often in the beginning that I played that my best players would get injured while playing a match that I win with 10-0 and the next day I would have a very strong league opponent or a qualifying match and my best players where most crippled.

So since I do it this way, I have less critical injuries, better overall team performance and improvement. Higher individual ratings overall too. Another bonus is that, because I train my team hard and a lot, after a few seasons they have improved in such a way that makes them easier to sell, simply because they outskill others. I even had 1 really succesful transfer deal, I bought 1 player for 17 million, played 6 seasons with him. and only sold him because he was getting too old for my selection , at the age of 28. He was sold for almost 38 million this season....... (Jan Kallen, two footed striker, with quite a nice stat sheet as for goals and assists in all the competions).

This season is one of my succesful financialwise, No money investments, halve way through the season, revenue (201 million) still in cup and CL. nr 2 in the league (lvl 10)

I've read about how many managers prefer very small selections....but for me this works best.

Answer to your question, I think they need rest from time to time ,`due poor endurance i guess.