Low made the assertion in the wake of Germany's Euro 2016 semi-final defeat to eventual runners-up France.
"I think 24 teams is too many," Low said to sportmasta1. "The World Cup is going to be increased to 40 teams and it is getting more and more.
However, Republic of Ireland manager O'Neill, whose team took four points from the world champions in Euro 2016 qualification, dismissed Low's comments.
"He has a moan about everything," O'Neill said, speaking as a pundit on TV3. "He had a moan about us the time we beat them in the game in October.
"He does like to moan a bit. He doesn't like to moan when they win the game themselves.
"With some of the bigger nations, it is a bit like it the FA when top sides didn't want to travel to non-league sides in case they were embarrassed."
Ireland came through a group containing Belgium, Italy and Sweden, but were eliminated at the round-of-16 by France.
O'Neill was happy with his players' overall performance at the tournament, but with 2018 World Cup qualification campaign starting in September, with Wales, Serbia, Austria and Georgia in the group, the Boys in Green boss is under no illusions about the task ahead.
"We’re in a difficult group and we don’t want to go out of the competition before it starts in that sense," said the former Celtic boss.
"These games are tough so our players will have to go and step up again.
"But will they have the confidence they didn’t have two years ago? Hopefully."