NSW Nurses and Midwives' Association Secretary Brett Holmes said staffing levels at the hospital are affecting patient safety and called for mandated nurse-to-patient ratios.

The nurses were striking from 2pm to 4pm on Friday.

"Nurses and midwives at Royal Prince Alfred Hospital tell us they are under enormous pressures every day. Excessive workloads are affecting their psychological and physical well-being, leading to high levels of staff turnover and burnout," Mr Holmes said in a statement.

He said chronic understaffing in the hospital's intensive care units meant some nurses are working excessive amounts of overtime.

The hospital remains open to the public while the strike action is underway.

The strike is the latest in a series of industrial actions by health staff in NSW in recent weeks, with some ruled unlawful by the Industrial Relations Commission.

It also comes amid the latest outbreak of COVID-19 in Sydney, which has prompted lockdowns in some parts of the city's centre and east.

Recent figures from the Bureau of Health Information for the January to March quarter showed NSW public hospitals are struggling to cope with demand.

Just over a quarter of patients - 27.6 per cent - were not treated within the clinically recommended time, an increase of 1.7 per cent.

The NSW government has been contacted for comment.

Australian Associated Press