"Paul O'Connell ruled out of Test series with undisplaced fracture of lower right arm," the tourists said in a statement via Twitter.
It's a bitter blow to O'Connell, who has spent much of the RaboDirect PRO12 season on the sidelines with a back injury, only to force his way into Lions contention with a some superb late-season performances, including that against Harlequins in the European Cup quarter-final victory.
O'Connell's absence will also be a major blow for the Lions - the Irish lock started all three Tests against New Zealand in 2005 and was made captain against South Africa in 2009.
England's Geoff Parling looks set to replace O'Connell in the starting XV for Saturday's second Test - he was due to captain the Lions in their midweek clash against the Rebels but he has since been withdrawn from the side.
A statement on the Lions' official website read: "Parling is the likely replacement for O'Connell at the Etihad Stadium this weekend.
"He was due to captain the Lions in their final mid-week match against the Rebels in Melbourne tomorrow but has now been withdrawn from the side."
Meanwhile, both Conor Murray and Simon Zebo have been named in the starting line-up against the Rebels.
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