Getting back in front of the cameras with co-host Philip Schofield, the presenter said: "It is really good to be back. I’m much better now, sorry about that, it really took me down."
Willoughby added that her son Chester, who she shares with husband Dan Baldwin, “wasn’t very well either”. “We’re fine now,” she continued, to which Schofield added: “Phew.”
The 40-year-old also thanked Josie Gibson, who stepped in for her last minute and covered for her during her absence.
“She did an amazing job,” said Willoughby. “All I did was watch you, it was a great show. I really enjoyed myself in my sickbed.”
“You missed the man with the biggest penis in the world," quipped Schofield, referring to a guest they had last week who shared some intimate pictures with the presenting duo.
“I did not, I watched it. I was glad I was at home," added Willoughby. "There’s something I can’t get out of my head," said Schofield.
Meanwhile, Gibson has opened up about her reaction to being asked to present the show last minute while she was already on her way to Surrey to present a competition segment.
"I couldn't believe it…” she explained. “I thought they had the wrong number, Phil. I said, 'You've phoned Josie.'"
She continued: “I’ve been thrown in the deep end, but I've got the best armbands on the planet. That's what I say.
"I just cannot believe I'm sat here, it is so surreal," she added. "I've grown up watching you, it's just crazy. What an honour."
Back on Wednesday, she explained she got showered with love by fans on social media.
“It’s really embarrassing, I did have a cry for about half an hour,” she explained.
“Well, I often do that after the show.”
Asked if it was because of relief, Josie explained she was emotional and that it was “a really big thing being sat here” and received many lovely messages.
Watch: Miriam Margolyes shocks Phillip Schofield and Holly Willoughby by breaking wind