Care home staff and nurses are among key workers facing the prospect of being paid less this year than last, according to the Trades Union Congress.
Pay increases are failing to keep up with rising inflation, leading to another year of "wages gloom" for public sector workers, the TUC said.
That could be a "hammer blow to morale" prompting staff to quit, it said.
The Treasury said that public sector wages would be going up for the next three years.
The TUC is calling on the government to ensure public sector workers receive a "decent" pay rise.
The union umbrella body said public sector workers were already thousands of pounds worse off after suffering a "lost decade", during which their pay failed to keep up with price rises.
With inflation now forecast to reach 6% or higher in 2022, the situation was set to get worse, it said.
Frances O'Grady, the TUC general secretary, said: "Hard work should pay for everyone.
"But millions of key workers - on the frontline of the pandemic - face another year of wages gloom. That is not right.
"The government must stop burying its head and get pay rising across the economy. Ministers cannot abandon families during this cost-of-living crisis."
In real terms - that is, after inflation is taken into account - nurses are £2,700 worse off than in 2010, the TUC has calculated.
Care workers employed by local authorities are more than £1,600 a year worse off, it added.
The TUC said excessive workloads and a lack of recognition, as well as stagnating wages, was causing a staffing crisis in the NHS and other public services, prompting staff to quit.
The body called on the government to prioritise key worker pay in 2022 by easing restrictions on pay policy and providing more funding to government departments.
A Treasury spokesperson said: "We recognise the incredible work that public sector workers have continued to do throughout the pandemic, and the challenges many of them have faced as key workers, and it's right that wages across the public sector will increase for each of the next three years.
"We have also backed public services with the largest real-terms increase in overall departmental spending for any Parliament this century."
The government is also raising the National Living Wage to £9.50 an hour from April and is providing £12bn this financial year and next to help families with the cost of living, including helping households with their energy bills.
Prices went up at their fastest rate in 30 years in the year to December, with inflation hitting 5.4%.
Soaring food costs and the energy bill crisis were the main factors driving price rises.
In December, the Bank of England predicted that inflation could hit 6% this year, but .