In 1989, Mesley married CBC news anchor Peter Mansbridge, but the marriage fell apart in 1992. She remarried on April 17, 1998 to marketing executive Liam McQuade and has one daughter with him, Kate Rae McQuade.
In January 2005, Mesley announced that she had found a lump in her left breast and had been diagnosed with breast cancer.
After undergoing treatment, including two lumpectomies, chemotherapy and radiation, Mesley's prognosis is excellent. As of March 2006, Mesley had returned to the CBC full-time, but was under the care of an oncologist and had been taking the intravenous, anti-cancer drug Herceptin. That same month her documentary "Chasing the Cancer Answer" was aired. Though generally well-received, it did engender negative comment from Margaret Wente.