McArthur looks almost certain to leave New Douglas Park after making what appeared to be an emotional farewell speech to fans after their last home game against St Mirren midweek.
Wigan appear favourites to land the 22-year-old after he revealed he would relish the prospect of joining forces with former team-mate James McCarthy again.
Reid lost both McCarthy and Brian Easton to the Premier League last summer - albeit Easton returned from Burnley on loan in January - but he believes McArthur will leave an even bigger void to fill.
"He's going to leave a huge dent," said the Accies boss.
"Not that he's better than the other two players but I said at the time, the one guy that I couldn't afford to lose was McArthur.
"Just what he brings to the team, I couldn't have done it without him. Alex Neil was out until November and McArthur became the captain and held us together.
"He has played a huge part in the five seasons I've been at the club and I'll never fill James McArthur's boots. He has been a fantastic professional for me."
Reid does not expect to be given cash from the sale of McArthur to fund a replacement, admitting he will be looking for a rough diamond instead.
He added: "I didn't get money last season to buy players, that's not going to happen at Hamilton Accies. I realise the club I'm working with and that doesn't concern me at all.
"We have to go and try to find another diamond and polish them up, find players that other clubs don't want and try to make them into players.
"That's just the nature of club I'm at. It's not frustrating because we know that's what's going to happen."
While resigned to the loss of McArthur, Reid is hoping to retain the services of Easton, Mickael Antoine-Curier, James Wesolowski and Joel Thomas, who all impressed while on loan this term.
"We don't know what's happening yet," he said.
"I've not put a timescale on it. They've got to go back to their respective clubs and then we'll have to see whether they want them to stay next season. There is a lot still to be decided.
"I would be looking to try to keep the four of them. Very much so.
"They have played a big, big part in what has gone on and I feel as though, if I can keep the majority of the squad together, we are in business for next season."
Accies head into Saturday's final game of the campaign hoping for the win that will take them above their opponents, St Johnstone, and allow them to claim seventh spot.
"It's a big game for both clubs," said Reid.
"They will want to finish above us. We did say, seven or eight weeks ago, when we were about seven or eight points behind them, that we would try to catch Aberdeen and St Johnstone.
"We are above Aberdeen, who can't catch us, and now we've got a shoot-out against St Johnstone to finish above them and that's how our players will be addressing the game.
"We are pleased with the way things have been going and we want to finish the season on a high."