The Denis Leary-starring series tells the stories of a group of New York firefighters.
Sarandon has signed on to portray Alicia, a rich, successful, older woman who seduces, Franco, played by Daniel Sunjata, The Hollywood Reporter said.
Her stint begins with the second episode of season three, which is currently under production.
"Rescue Me" is expected to return to FX sometime in early summer.
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