Paul O'Connell has become the latest Ireland player to be ruled out of the Test against South Africa on Saturday.
The Munster lock had to withdraw following of a recurrence of his back injury on Wednesday.
Irish management said O'Connell took part in full training sessions on Monday and Tuesday, but had then suffered a reaction to the injury.
Ireland are already without Brian O'Driscoll, Stephen Ferris, Rob Kearney, Rory Best and Sean O'Brien.
Coach Declan Kidney did have some good news this week when Leinster prop Cian Healy was declared fit after recovering from a shoulder problem.
O'Connell had been expected to captain Kidney's men at the Aviva Stadium in the absence of O'Driscoll.
Ireland have yet to announce who will lead the team and they could opt for Jonathan Sexton or Jamie Heaslip with one eye on the future.
Simon Zebo and Denis Hurley are competing for the full-back duties with Keith Earls replacing O'Driscoll at outside centre.
Ireland are expected to name their team at Thursday lunchtime