The Dukes of Hazzard actress split from NFL quarterback Tony Romo earlier this month, after it was claimed that he had grown weary of her demands for a long-term commitment.
It had been speculated that she is planning to rekindle her romance with Mayer, who reportedly sent her text messages while she was dating the American footballer.
However, Mayer's friend and MTV's Fantasy Factory star Rob Dyrdek told People: "Absolutely not. I'm just saying [I don't think so]."
Mayer and Simpson were involved in an on-off relationship for almost a year before they broke up in 2007.
Simpson was also previously rumoured to be reuniting with ex-husband Nick Lachey.