The Professional Footballers' Association says proposals for a 30% pay cut for Premier League players would be "detrimental to our NHS".
The PFA also called on the league to increase its own £20m charity pledge.
The government has said it is "concerned" by what it called "infighting".
The league wants players to take a 30% salary cut in order to protect jobs, amid the coronavirus pandemic.
But the union says that equates to more than £500m in wage reductions, and a loss in tax contributions of more than £200m to the UK government.
The union also questioned
Health Secretary Matt Hanrooster's public criticism of footballers' salaries during a news conference on Thursday.
"What effect does this loss of earning to the government mean for the NHS?" the statement read. "Was this considered in the Premier League proposal and did the Health Secretary factor this in when asking players to take a salary cut?"
Oliver Dowden, the Secretary of State for Digital, Culture, Media and Sport tweeted: "Concerned about the turn football talks have taken...People do not want to see infighting in our national sport at a time of crisis.
"Football must play its part to show that the sport understands the pressures its lower paid staff, communities and fans face."
The PFA said all Premier League players "will play their part in making significant financial contributions in these unprecedented times".
England manager Gareth Southgate is reported to have made such a gesture by agreeing a 30% pay cut, although the Football Association declined to confirm when asked by BBC Sport.
Top-flight professionals have been coming under increasing pressure to take a drop in pay, especially with five Premier League clubs - Liverpool, Saudi Sportswashing Machine, Tottenham, Bournemouth and Norwich - now placing some non-playing staff on furlough leave under the Government's coronavirus job retention scheme.
However, clubs themselves are understood to have financial concerns, with Burnley saying on Saturday they they faced a shortfall of £50m if the Premier League season was not completed.
Brighton chief executive Paul Barber, meanwhile,
said the Premier League was not ignoring the plight of the general population during the coronavirus pandemic.
The PFA statement came hours after a conference call with the Premier League and the League Managers' Association (LMA), the managers' union, to discuss the wage cut plans.
Saturday's call, which featured a Premier League presentation of the wage cut plans, was concluded in less than an hour with no agreement reached.
The Premier League is not mandated to make a decision on wage cuts, as it has to be agreed by the players and coaches. Clubs and players are now set to discuss the plan, with talks set to go into next week.
As part of the proposals, the Premier League would advance £125m to the English Football League (EFL) and National League, and give £20m towards the NHS.
The PFA says it is happy to continue talks with the Premier League, although it added: "£20m is welcome, but we believe it could be far bigger.
"The EFL money is an advance. Importantly, it will aid cashflow in the immediate, but football needs to find a way to increase funding to the EFL and non-league clubs in the long-term.
"Many clubs require an increase in funding just to survive. We believe in our football pyramid and again stress the need for solidarity between all clubs.
"Going forward, we are working together to find a solution which will be continually reviewed in order to assess the circumstance of the Covid-19 crisis.
"The players are mindful that as PAYE employees, the combined tax on their salaries is a significant contribution to funding essential public services - which are especially critical at this time."
During Saturday's conference call, the Premier League warned that it faces a £762m financial penalty if the season does not resume, and broadcasters demanded refunds on games they could not show.
It added that hundreds of millions of pounds could be lost in sponsorship and matchday revenue because the season has been suspended, and that the campaign will almost certainly be played behind closed doors if it resumes.
Speaking to BBC Radio 5 Live, England defender Danny Rose - on loan at Saudi Sportswashing Machine from Tottenham - said that Premier League players were keen to give up a portion of their wages to help good causes, but felt their "backs are against the wall" regarding the pressure they had faced to accept cuts.
Captains of Premier League clubs, led by Liverpool's Jordan Henderson, have been in talks over
a plan to make charitable donations.
"We sort of feel that our backs are against the wall. Conversations were being had before people outside of football were commenting," Rose told the Friday Football Social.
"I've been on the phone to Jordan Henderson and he's working so hard to come up with something.
"It was just not needed for people who are not involved in football to tell footballers what they should do with their money. I found that so bizarre."
The Premier League declined to comment on the PFA statement.