Liverpool manager Jurgen Klopp said the Premier League's top six could be left without 11 fit players unless changes are made to protect the welfare of stretched squads.
Already depleted by an injury crisis, the Reds will play three games in six-and-a-half days this week.
Klopp's men saw off Leicester City 3-0 in Sunday's late Premier League kick-off and will welcome Atlanta to Anfield in the Champions League on Wednesday before travelling to Brighton for Saturday's 12.30GMT kick-off.
"If we keep playing Wednesday night and Saturday 12.30, I am not sure we finish the season with 11 players, all the top six or seven," said Klopp in an impassioned interview with Sky Sports, the largest domestic rights holder of Premier League games.
Under the terms of a £4.5 billion ($6 billion) deal for three seasons, Sky have the first pick from each round of games with BT Sport choosing their headline match second.
But Klopp said broadcasters should adapt to the circumstances of a season like no other, with matches crammed into the calendar to make up for the lost time of a three-month postponement to last season due to the coronavirus pandemic.
"Everybody tells me it is difficult, but it is difficult for the players. That's what is difficult. The rest is just a decision on a desk in an office," added Klopp.
"If someone tells me again about contracts I go really nuts because the contracts were not made for a Covid season.
"We all have to adapt. You stand here with a facemask, would you have thought a year ago you would go somewhere with a facemask and we cannot be close? That's the situation. Everything changed, but the contract with the broadcasters is still 'we said this so we keep this'."
Manchester United manager Ole Gunnar Solskjaer said his side had been "set up to fail" when faced with the same situation earlier this month when they travelled back from facing Istanbul Basaksehir in the Champions League on a Wednesday night before a lunchtime kick-off away at Everton.
Klopp claimed to even have considered sending a youth team to Brighton to prevent more injuries.
Virgil van Dijk, Joe Gomez, Trent Alexander-Arnold, Jordan Henderson, Thiago Alcantara, Xherdan Shaqiri and Alex Oxlade-Chamberlain missed the win over Leicester, while Mohamed Salah was absent due to a positive coronavirus test.
"We will go there shaking," said Klopp. "I think about sending the points."
And the German stressed his complaints are not based out of self-interest.
"It was never about us when I spoke about it, it's about all the players. It's about the England players, all the players who play the European championship in the summer," he continued.
Klopp and Manchester City boss Pep Guardiola have been outspoken campaigners for the Premier League to return to using five substitutes, like all other major European leagues and the Champions League.
However, when City and Liverpool faced each other earlier this month, only three of the possible combined six changes were made, while Klopp used two of his three substitutions against Leicester in the final minute.
"Why we have to change late is we constantly have to think that someone will go down," Klopp explained.
"We cannot change early because another one has a muscle injury and you end the game with nine players."
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