Reviewing the papers with guests Jonathan Wilkes and Lizzy Cundy, the foursome discussed a poll which claimed that a third of Britons do not know where the UK's three biggest cities - London, Birmingham and Glasgow - are on a map.
When Wilkes admitted that he is "in that third", Holmes used the word in response, prompting laughter from the other three.
Apologising after a break, the Sky News presenter said: "Sorry to three or four of you who have got in touch this morning, because I used the word 'retarded' during the newspaper review.
"You seem to take it personally or seem to say that I'm insulting all sorts of people who have all sorts of conditions."
The 51-year-old, who was presenting the daytime magazine series alongside wife Ruth Langsford, said that he did not know what word he would have used instead, adding: "But obviously I would never want to do that or cause any sort of offence.
"There's this man who has got an autistic son, who said that somehow I had insulted his child. I really hope it hasn't, because I certainly wouldn't use it in that context. Sorry if that caused you offence."
Writing on Twitter, Holmes thanked followers for their "support and understanding", continuing: "We all make mistakes. Those who want to find mischief will push things."
An ITV spokesperson told Digital Spy: "Eamonn accepts that it was a poor choice of words and it was not his intention to cause any offence. He has apologised on air for any offence caused."
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