Northern Ireland take on Uruguay, who are in England's World Cup group, on Friday, but the hosts will be without the Premier League Player of the Year after he underwent knee surgery last week.
The manager told BT Sport: "It would have been terrific for the players to come up against Luis Suarez, particularly for some of the younger lads who will start the Uruguay game.
"It is always good to challenge yourself against the best in the world like we did against Cristiano Ronaldo in the World Cup qualifying campaign.
"If I'm being honest, though, I'm not exactly devastated Suarez won't be fit enough to face us. He is a big, big part of their team and it will be interesting to see how they cope without him."
O'Neill's side will also face Chile during their tour of South America.