A quarter of staff sick days in Robert Jones and Agnes Hunt Orthopaedic Hospital were due to stress-related reasons, new figures show.
The King's Fund, a health think tank, said the high level of stress-related absences is a "wake up call" for the NHS to address excessive workloads on staff.
Latest NHS Digital figures show there were 2,600 days lost due to staff absences in The Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust in February.
Of the days lost, 608 were due to anxiety, stress, depression or other psychiatric illnesses. It accounted for 24% of staff sick days and was the most reported reason for sickness.
It was down from 28% in February the year before, but was an increase from 15% in 2019, before the pandemic.
Across England, anxiety, stress, depression and other psychiatric illnesses accounted for over 545,100 days lost and 26% of all sickness absences in February.
It was up from 25% the year before and a jump from 23% in 2019.
Alex Baylis, the King's Fund assistant director of policy, said: "This is just another wake up call to the NHS, because we are seeing exactly the same sort of trends when you look at reasons for people leaving the NHS."
He said the normalisation of "chronic excessive workloads" on staff is the main driver in the high levels of stress-related sick absences.
He added: "So, what we think is important is not just focusing on supporting individuals but looking at what these systemic, underlying drivers of these levels of stress and burnout.
"That means really listening to staff and being prepared to put in place fundamental changes where needed to address this, rather than normalise it and carrying on with these constant warning signs we are getting."
The figures also show the overall sickness absence rate for England was 5%. At The Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, the absence rate was 6%.
The Nuffield Trust said high sickness absence is detrimental to staff and patient care.
Billy Palmer, Nuffield Trust senior fellow, said: "The NHS has a duty of care to its workforce, and this high level of stress among staff also points to some troubling future retention issues.
"Given high sickness absence levels and poor retention are both causes of and caused by increased pressure of services, the NHS risks being stuck in a vicious cycle."
He added absence rates relate to factors including job satisfaction, workload and socioeconomic status, so multiple solutions will be needed to solve the levels of sickness absence.
An NHS spokesperson said mental health support is available for staff, including access to 24/7 confidential support services, coaching, and flexible working options.
They added "there is more to do" to ensure NHS staff feel comfortable asking for help.
"That is why the NHS is strengthening our occupational health services and reviewing our mental health offer for staff to ensure everyone working in the NHS has the right support they need," they said.