The comedian was on the BBC show to talk about turning 60 – but viewers were distracted by his appearance.
One viewer tweeted: “Poor Lenny Henry doesn’t look well at all. Hope he's ok. #theoneshow.”
Another wrote: “What's happened to our Lenny he looks seriously ill? #theoneshow.”
A third referenced his Premier Inn adverts, posting: “And Lenny has clearly been missing out on those Premier Inn breakfasts! #theoneshow.”
Henry first debuted his slimmer frame in June at a special gala performance of the The Jungle at the Playhouse Theatre.
Opening up about how he shed the pounds he said at the time: “What’s my secret? Well, it’s eating broccoli and not much else.
“I’ve also been running a lot. It has worked!”
It’s not the first time he has lost weight, having dropped three stone after splitting with his wife Dawn French in 2011.
Henry was on Monday night’s The One Show ahead of his 60th birthday on August 29. Opening up about his plans for the milestone occasion he said he is have a “bit of a do” with “pies and prosecco”.
Henry praised Madonna, who turned 60 last week, for proving that age is just a number – but joked reaching his sixth decade is problematic for his wardrobe.
“She’s the living proof that you can keep going,” he said. “The only problem is – what do you wear now? I was going to wear a Wu Tang clan tracksuit but I looked at myself and thought ‘don’t be ridiculous’.”
British Paralympian Lauren Steadman was also on the show to confirm her place on this year’s Strictly Come Dancing.