The 31-year-old defender aggravated a calf injury late in the first half of the 1-0 Barclays Premier League defeat by Manchester United, and O'Neill later admitted he could be a doubt for Poland and Ukraine.
"John didn't feel comfortable. He has come back and he was starting to feel his injury, so he just didn't feel confident at all about moving on it," said O'Neill.
Asked if that could jeopardise his chances of representing the Republic this summer, O'Neill added: "It might do.
"As he came off, that was my thought, that there might be a concern about it.
"I haven't had a chance to check with the physios since that. Maybe I am jumping the gun, but it might be a concern."