Brian joined Holly and Phillip Schofield in the studio alongside Adam Lambert and drummer Roger Taylor, discussing their latest music venture.
However, the mood changed when the 73-year-old rock star shut down questions about recent comments made by Chancellor Rishi Sunak, insisting he felt he had been misquoted.
Holly said: "Chancellor Rishi Sunak appeared to suggest in an interview with ITV news that struggling musicians and artists ought to retrain and get a new job.
"I just thought for musicians like yourself, Brian, and all of you, how you felt, like, if somebody had said to you in your career, well ‘do you know what there's no live music any more so go and retrain and do something else'."
She asked: "How do you feel about that?"
Brian then suggested the chancellor had been misquoted, as he reflected on his own initial response to the statement.
He said: "You know honestly I saw it last night and I had a knee jerk reaction and I wrote this kind of Instagram thing saying ‘why don't you go and retrain again'.
"And then I thought ‘actually, did he really say that? And I actually checked and I saw the transcript so I don't think he said that, to be honest."
Holly then read out the quote from the chancellor, which said: "I can't pretend that everyone can do exactly the same job that they were doing at the beginning of this crisis.
"That's why we've put a lot of resource into trying to create new opportunities."
Hitting back, Brian replied: "Yeah but he doesn't specifically say musicians should go out and get another job, I don't think so.
"I know because I get misquoted so much and people kind of bend the quotes so I'm a little wary of jumping on people. Obviously, I don't want to get another job, and on the face of it it was insulting, but we're okay.
"Our industry has been hit hard but every industry has been hit hard, we just make the best of it."
Over on Twitter, viewers were quick to praise Brian's speedy rebuttal, as they watched the daytime show from home.
One said: "I'm glad Brian put Holly in her place after she tried to force a headline through misquoting."
"Here we go again why bring politics into talking to Queen. Thank god Brian May wouldn't be led," added a second.
And a third wrote: "Love Queen put Holly firmly back in her box. Mis-quoting people forcing a story."
Brian also paid tribute to a legend of the rock world on today's show, following news of Eddie Van Halen's tragic death on October 6.
Honouring the musician's legacy, Brian said: "I've got to say I'm feeling really gutted this morning at the loss of Edward Van Halen. I can't really get that off my mind."
This Morning airs on weekdays at 10am on ITV.