"I don't even know how to feel about that. I'm like, 'Wait a second. If I have to be upfront a herpe, how could you not be upfront about HIV?" she questioned, suggesting there had been a double standard on their time together filming Two and a Half Men.
But in an exclusive statement to PEOPLE, Sheen's manager Mark Burg says: "Charlie was infected long after he left Two and a Half Men and long after he worked with Jenny."
McCarthy, 43, played one of Sheen's love interest for eight episodes of the hit CBS show from 2007-2011. However, Sheen has maintained he wasn't diagnosed with HIV until after his run on the show. He went on to star in Anger Management from 2011-2013.
McCarthy went on to reflect further about her days on the show given what she knows now.
"Playing his love interest on the show, even back in the day, I go, 'Ick! That's not fair. It's scary.' I have sympathy for him because, you know, he's sick and it's awful, but man he's going to have some major accountability with many people in his life," she said.
RELATED VIDEO: VIDEO: Charlie Sheen Reveals He Was Diagnosed with HIV 4 Years Ago and Says He Has Paid $10 Million in Extortion
Sheen, 50, told the Today show's Matt Lauer he was coming forward with his diagnosis after being "extorted" for upwards of $10 million by people trying to sell his story. Sheen told Lauer he has not passed on HIV to any of his partners and that he told his former lovers about his diagnosis.
On Wednesday, civil rights attorney Gloria Allred suggested that some of his exes have reached out to her about potential legal action.
"Since Charlie Sheen's interview yesterday, I will now confirm that I have been contacted by women with reference to Charlie Sheen and their rights," she said in a statement to PEOPLE. "I have no comment on what will happen next."
On Tuesday, Sheen's ex Bree Olson lambasted the actor for not revealing his HIV-positive diagnosis during her stint as one of his live-in Goddess girlfriends in the Spring of 2011. But his manager Mark Burg told PEOPLE exclusively Sheen was "100 percent HIV-negative," in early 2011 when the actor and Olsen were together. Burg added that Sheen actor was tested for the virus on numerous occasions around that time.