The Friends star posted a long message to fans on Instagram, saying she understands masks are “inconvenient and uncomfortable” but that people should wear them if they “care about human life”.
Cases of COVID-19 are on the rise in parts of the US, including in the star’s home of California.
New coronavirus cases in the state rose by 8,441 on Tuesday, according to a tally by news agency Reuters – the highest single-day increase since the start of the pandemic.
The US as a whole also saw its biggest one-day spike in new infections on Tuesday, with more than 47,000 cases.
Texas and Arizona, as well as California, have emerged as new epicentres of the pandemic.
Wearing a mask is mandatory in many public places in California, where bars have been forced to close only weeks after reopening, and beaches have been shut ahead of 4 July celebrations on Saturday.
Sharing her thoughts on social media, Aniston, 51, wrote: “I understand masks are inconvenient and uncomfortable.
“But don’t you feel that it’s worse that businesses are shutting down… jobs are being lost… health care workers are hitting absolute exhaustion.
“And so many lives have been taken by this virus because we aren’t doing enough.”
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She continued: “I really do believe in the basic goodness of people so I know we can all do this BUT still, there are many people in our country refusing to take the necessary steps to flatten the curve, and keep each other safe.
“People seem worried about their ‘rights being taken away’ by being asked to wear a mask. This simple and effective recommendation is being politicised at the expense of peoples’ lives. And it really shouldn’t be a debate.”
Aniston added: “If you care about human life, please… just #wearadamnmask and encourage those around you to do the same.”
Dr Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, has warned that the number of cases across the US could increase even further.
He told a US Senate committee he is “concerned” because the situation could become “very bad”.
“We can’t just focus on those areas that are having the surge,” said the country’s top infectious diseases expert.
“It puts the entire country at risk.”