The former Bridgend star will miss the games against Australia, South Africa and Fiji and has been given only an outside chance of making the final Test against New Zealand on November 27.
But while assistant coach Howley admits it is disappointing to lose a player of the 29-year-old's quality, he is confident that Chris Czekaj can plug the gap having been called up to the autumn squad this week.
"Lee's a British & Irish Lion. His kicking game is one of the best in the northern hemisphere and he's solid under the high ball," said Howley.
"I think he started slowly but has played particularly well in the last few games for the Ospreys. Your fullback is your best defender and we're disappointed to have that injury.
"But we're also delighted to bring Chris Czekaj in. He he's been playing well. He was omitted from the squad and will have a point to prove and it will be interesting to see how he goes in training.
"He is strong under high ball, works hard off the ball and is very physical. We were a little bit disappointed with his condition and that is one of the reasons we originally omitted him. But he's got another opportunity and will be hell bent on proving us wrong."
Howley also admitted that moving James Hook back to 15 just as was the case in last year's Autumn Series could be another option.
Hook featured at full back this time last season but was then moved into the centre by both club and country.
The 25-year-old was a sensational success at 12 and 13, winning plenty of plaudits as the Ospreys claimed a third Magners League crown and Wales picked up Six Nations victories over Scotland and Italy and then ran South Africa close in June.
"Hook played 15 in the last Autumn Series when Byrne was out," added Howley.
"The decision is about whether to give Hooky the opportunity to be the best 12 or 13 in world rugby or putting him back to 15.
"It isn't about James Hook, it's about what's best for the team and the balance of the backline. We all know about James' creativity and intuitivism. He is one of the best players in the world. But the decision will be what is best for Wales and him.
"But we have got other options. That's why we brought Czekaj in, plus there's Tom Prydie.
"There's a multitude of options and it's not necessarily who's the best 15 but who fits the dynamic of the team best."