The Wales and Lions Test full back sustained an injury to his left thumb at training in Cape Town to add to the problems he experienced with his left foot in last weekend's first Test in Durban.
After consultation between the Lions and Ospreys' medical staff he will return to Wales into their care in the next few days for further specialist opinion and treatment. With just two matches remaining on the tour the Lions will not be calling for a replacement at this stage.
"I'm very disappointed that I got injured in training today and that my tour is over. I was recovering from my foot injury and was taking part in training when I hurt my thumb in a freak accident," said Byrne.
"To be ruled out of the tour at this stage with just two matches left is devastating. Returning home immediately is the right thing to do as it means I can get the right medical treatment straight away.
"I wish the boys all the best for the rest of the tour."
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