For eight episodes of the hit CBS show, the mother of one played one of Sheen's love interests, named Courtney, from 2007-2011.
Sheen, 50, revealed earlier this week that he was dignosed with HIV positive four years ago.
She expressed her concerns on a show, saying "it's scary" and "not fair" to have portrayed his girlfriend knowing what she knows now.
Recalling her time with Sheen, the actress said, "Before we do a job, we have to sign a piece of paper that says, 'Do you have cold sores?' I'm like, 'Wait a second. If I have to be upfront a herpe, how could you not be upfront about HIV?' I look back and I'm like, that would have been valuable information. I mean, look how many people have played his love interest on the show."
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The actress later expanded on her previous statements noting a double standard in Hollywood.
"Every actress (and actor for that matter) must disclose hundreds of personal health matters before ever being allowed to set foot on a film set," she shared on Twitter.
"The point I raised about Charlie Sheen on my Sirius radio show, had nothing to do with whether or not I think he put me at risk," McCarthy, 43, clarified in the tweet.
"Yet an actor who interacts physically with dozens of actresses in intimate scenes, is not required to disclose that he has HIV? I am very aware that HIV is not spread through kissing, but I also believe that if an actress has to disclose all of her business before kissing a male costar, that actor should be required to disclose something (as) major as an HIV infection too," she wrote.