Up to nearly one in four ambulance staff in parts of the country took time off work because of stress in the last financial year, according to new figures.
One in eight workers across England took a total of 80,000 stress-related days off in 2016-17, said the GMB union.
Its Freedom of Information request to ambulance trusts covering paramedics and healthcare assistants showed that 23% took time off in the East Midlands and 22% in the North East.
GMB national officer Kevin Brandstatter said: "These disturbing figures once again prove what we already know - that our frontline ambulance workers are in the midst of a stress and anxiety epidemic.
"They are consistently overworked, underpaid and expected to do incredibly difficult jobs, such as dealing with the aftermath of the Grenfell disaster or Manchester bombings, without adequate staff or resources.
"Theresa May needs to stop burying her head in the sand and start listening to frontline ambulance workers.
"Workforce numbers haven't kept pace with sharply rising demand. Forcing ambulance staff to work up to the age of 68 is another major cause of stress.
"There's no justification for treating paramedics differently to comparable physically demanding frontline roles.
"The absences caused by staff shortages and overwork are already contributing to potential delays in attending incidents.
"If any patients lose their lives as a result, the blame falls fairly and squarely on an uncaring Tory Government for not dealing with stress and anxiety of our frontline emergency staff."
A Department of Health spokesman said: "Our dedicated paramedics do a vital and challenging job, and in recognition of their heroic responsibilities we've agreed a deal with unions to move them further up the NHS pay scale, increasing the maximum they can earn by 25%.
"We're also helping existing staff workloads by recruiting 2,600 more paramedics since 2010, as well as training record numbers of new paramedics."