Special Minister of State Don Harwin and Local Government Minister Shelley Hancock have both told Mr Perrottet they do not want to be considered for a role in the reshuffle and will not contest the next election.
Mr Perrottet said they have both "been strong advocates for the people of NSW in their respective roles as ministers throughout their careers" and wished them well as they "continue to do what they do best by serving the great people of NSW", even outside of parliament.
Mr Harwin has been "giving consideration to whether I could commit to another eight-year term".
"I have now decided I will not recontest my seat and therefore, this is the right time to end my ministerial service," the long-standing MP said in a statement on Saturday.
Mr Harwin was first elected to the state's upper house in 1999 and has held ministries including energy and utilities, resources, public service and employee relations, Aboriginal affairs, heritage and the arts.
He has also been special minister for state since 2017 and leads the government in the upper house.
Mr Harwin said "at this stage" he plans to finish the remainder of his term in the upper house and bow out at the next election.
Ms Hancock first joined parliament in the legislative assembly in 2003, where she later served as speaker for close to eight years before her current ministry role.
Ms Hancock says "challenging family circumstances" and the departure of Gladys Berejiklian, who resigned as premier in October ahead of appearing before the Independent Commission Against Corruption, influenced her decision to step down.
She described the former premier's resignation as "a loss for New South Wales and a personal loss for me, and something that I have found difficult to move past".
Ms Hancock says the premier who replaced Ms Berejiklian needs to have more women in his cabinet.
"It is often difficult being the only woman in the room, or one of a handful, therefore it is essential that women make up a larger part of the cabinet to provide our views and perspectives," Ms Hancock said.
On Saturday evening, it was confirmed long-serving Nationals MP Melinda Pavey has been dumped from cabinet, the third casualty of the reshuffle.
Ms Pavey, the most senior woman in the lower house, said she would continue to serve for her party.
"I'm incredibly proud of the billions of dollars in funding that I secured for country timber bridges and local roads in the roads ministry, the record amount of public housing and the reforms that I made in the Murray Darling Basin plan," she told The Daily Telegraph.
"I will continue to serve and be a team player."
The soon-to-be-shuffled cabinet includes five women, including Ms Hancock, across 21 positions.