Compulsory breaks to prevent player burnout are urgently needed, world players' union FIFPRO have said.
Their 2020-21 workload report for men's football shows top professionals are now playing more than two-thirds of their minutes in a season in the 'critical zone' - appearances of at least 45 minutes in matches less than five days apart.
Cumulative exposure to such back-to-back action can lead to greater risk of injury and affect the length of a player's career, FIFPRO said.
The union have proposed a player should miss a game after as few as three matches in the critical zone.
For a Premier League player, this could mean a reduction of between two and eight matches per season across club and national team duty. The report noted one way could be to rest players in domestic cup games, predominantly 'secondary' cup competitions like the Carabao Cup in England.
"The argument for scrapping the competition altogether comes up time and time again," the report said.
"These secondary cups could also be reimagined as under-23 competitions."
The report is based on data from about 40,000 appearances by a sample of 265 male players from 44 leagues between June 2018 and August 2021.
For players at national team level at the pinnacle of the game, 67 per cent of their minutes in the 2020-21 season were played in the critical zone, up from 61 per cent in the previous two seasons.
It highlights the case of Manchester United and Portugal playmaker Bruno Fernandes. Between November 2020 and April 2021 his share of minutes in the critical zone did not drop below 68 per cent and was close to 100 per cent on multiple occasions.
FIFPRO general secretary Jonas Baer-Hoffmann said: "The data shows we must release pressure on players at the top end of the game and this report provides new research why we need regulation and enforcement mechanisms to protect players.
"These are the type of solutions that must be at the top of the agenda whenever we discuss the development of the match calendar. It's time to make player health and performance a priority."
Baer-Hoffmann said such safeguards need not lead to star players missing big matches, if sufficient forward planning was carried out.
He added: "It is far less problematic to do it this way than to wait for the muscle tear to come, and then the player is out six weeks and nobody sees them, which ultimately harms the competitions and the fan experience more."
He said he was "not convinced" by the argument that such safeguards would lead to a greater stockpiling of talent by the clubs with the greatest financial resources, and said a squad of 25 with rotation would probably be sufficient to protect players from burnout.