Covid-19 is surging in parts of the US, including in Aniston's home of California, where bars have been forced to close only weeks after reopening.
The famously sunshine-filled state - where wearing a mask is mandatory in many public places - has also closed its beaches ahead of Fourth of July celebrations on Saturday.
Aniston, best known for playing Rachel Green on beloved comedy Friends, shared a selfie in a mask alongside a message urging fans to cover up outdoors.
"I understand masks are inconvenient and uncomfortable," the actress wrote.
"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."
While California governor Gavin Newsom made wearing a mask in many public places mandatory, the practice remains controversial for some, who refuse on the grounds of personal choice.
Aniston, 51, said the issue has been politicised.
She wrote: "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 wear a damn mask and encourage those around you to do the same."