The presenter had apparently asked Sinead for an interview for his show Uncensored which prompted a withering reply from the fiery performer.
Taking to Twitter, 55-year-old Sinead shared a screenshot of the email she sent back to the former Good Morning Britain host.
She captioned the image: "Piers Morgan's been trying to get me on his breakfast show since Shane died. Here's what I emailed him in response: Hopefully you'll chortle your tea out your nose."
She wrote: "Hi Piers, I think it's best I don't do your show because of the irresistible temptation I would have to point out that you're dying to be balls deep in Meghan Markle so bad it's driven you crazy."
The Tweet continues: "It being the case that if you were ever to get near her, which would never happen, you'd last ten seconds: and that would be that for ten days."
Piers was quick to respond with his own tweet that reads: "Hi Sinead, a delight to hear from you and I did indeed chortle my tea out of my nose.
" Three things.. a) I haven't hosted a breakfast show for a year. b) I actually fancy you, not Meghan. Think it's the GI Jane hair thing. c) I was so sorry about your son. Hope you're OK."
Fans left dozens of replies, applauding Sinead for her biting remarks with one writing: “Oh god what a wonderful feeling that must have been to send that answer back, you make my day.
“After he has read your answer he will think. No, I shouldn't have done that last whiskey.”
Another added: “Okay, this made me actually roar out loud with laughter.”
One person said: “this is the funniest thing I’ve seen all week while another added: “There is literally NO coming back from that!!!!!!!”
One other fan wrote: “Oh my GAWD. Sinead, you are one of a kind and we love you for it.”
Distraught Sinead recently emailed Taoiseach Michael Martin, demanding that both he and President Michael D Higgins issue an apology to her for the State's failure to attend the funeral of her son Shane.
Shane O’Connor died by suicide earlier this year. At the time of his death, Shane was in the care of the Irish State.
The 17-year-old’s body was found in Bray just days after he went missing from Tallaght Hospital in January.
Taking to social media, Sinead shared screenshots of a lengthy email she penned to Taoiseach Michael Martin.
“I’m Sinead O’Connor, the singer. My 17-year-old son, Shane, died while in the care of the Irish state,” she began.
“I want to know why the state were not represented at my son’s funeral and why the Irish State have a policy of non-attendance at the funerals of the scores of yearly funerals of the children who are dying in its custody.
“I want to know why no one representing the Irish State has formally either publicly or privately sent apologies or condolences to the mothers of whom the state promised to take better care of than we could.”
“I know my child wouldn’t be dead if the State had ever cared about keeping that promise,” she said.
She continued by saying that she warned the State for four years that her “child wouldn’t make it to 18 if they didn't get their act together.
“I asked them ‘do you really want Sinead O’Connor’s son to die on your watch?’”
“Point being I have absolutely nothing left to lose and there's nothing the State can frighten me with."
The Hindu funeral of her son which took place on January 13 was attended only by Sinead and his father, musician Donal Lunny.