Marta Temido has been broadly criticised over her handling of recent staffing problems at public hospitals.
Portugal's health minister has resigned amid criticism that hospitals in the country have been short-staffed this summer.
Marta Temido said on Tuesday that she felt she could "no longer remain in office," according to a government statement.
The 48-year-old was appointed Portugal’s health minister in 2018 and was one of the most popular members of the centre-left Socialist government during the COVID-19 pandemic.
But she has been under severe pressure for several months -- including from within her party -- due to temporary closures of public hospital emergency services.
Many health facilities, including emergency and maternity departments, have been forced to shut their doors due to a lack of staff.
Critics have accused the health ministry of failing to plan for the staff shortage during the summer when many people take holidays from work.
In one notable incident, a pregnant woman from India died on Saturday while being transferred between two Lisbon hospitals, as the first had reached its maximum capacity.
Groups representing Portuguese doctors and nurses have also been critical of Temido’s policies, citing poor working conditions and extreme fatigue.
The Socialist government says it will push ahead with reforms to strengthen the country's health service, but has not announced Temido's replacement.
"Prime Minister António Costa thanks Marta Temido for all the work she has done, especially during the exceptional period of the fight against the covid-19 pandemic," a brief statement read.