Everton's James McCarthy and Newcastle's Daryl Murphy could miss out too with Ireland rapidly running out of options, although their manager is confident he will still be able to field a competitive team.

Asked for an injury update, a frustrated O'Neill said: "How long have you got? It's the lengthiest list of injuries that I have known since I have come into the job, and unfortunately it's happened at a really crucial time for us.

"However, other players will have to step up and just be ready for Friday. Do you know, I have often said this before, that you just curse your luck and get on with it.

"The irony of all of this here is that way back when Gareth Bale got injured in November-time, everybody was talking about Wales possibly having one of their major players out of the team, and it turns out that we are the ones who are doing the suffering.

"But it is what it is and we'll get on with it and we'll be ready to go on Friday."

The Republic head into the game sitting proudly at the top of Group D and four points better off than Euro 2016 semi-finalists Wales.

It would have been a tough enough test even with a full-strength squad and while victory for Ireland would significantly strengthen their qualification hopes, defeat would drag Chris Coleman's men right back into the thick of the fight.

O'Neill said: "Wales will not feel as if they're out of it at all by any stretch of the imagination. Their own experiences of the Euros will stand them in good stead.

"This game has come at a time when we've had to look at some of the major players being out, but we'll go with it with as much gusto as possible."

Ireland's challenge will be increased markedly by the presence of Bale in the Welsh squad following his recovery from ankle surgery, and while O'Neill knows they are far from a one-man team, he is well aware of the threat the Real Madrid star poses.

"Bale is an absolutely top-class player," he said. "He's into the world-class bracket. He has proved that, winning Champions League medals with Real Madrid. He left Tottenham, where he was a real star, and he has gone to prove himself with Real Madrid.

"He's a really fine player, there's no question about that. Wales have got some really fine players besides that who are playing at a big level and they are coming here relatively injury-free.

"It's a tough task. It would have been a tough task normally even if we were at full-strength. It's going to take an almighty effort to win this game."

Striker Jonathan Walters has been around the Republic squad long enough to know they are often at their best when their backs are against the wall, and is hoping the same applies this week.

Walters said: "Over the course of the past few years, we've been underdogs in a lot of games and got the result we wanted.

"We showed that in the summer [at Euro 2016], such a difficult group to get out of and we did, and we've shown that in this campaign so far.

"It's another difficult group to get out of, but four games in we're sitting pretty at the moment."