Leinster loose-forward O'Brien is a major doubt for the RBS 6 Nations after dislocating his shoulder in Saturday's 19-6 win over Ulster.
Openside Henry tore his hamstring in Ireland's 40-9 victory over Samoa in Dublin at the start of the autumn international series.
The 29-year-old has found fitness in time for Friday's RaboDirect Pro12 clash with Munster at Ravenhill, and admits his return could prove timely for his Ireland chances.
"It is devastating news for Sean O'Brien," Henry told The Score website.
"For myself, it is about getting back in the Ulster team and putting in the performances here, one week at a time.
"Hopefully I'll do enough to get into the Six Nations squad.
"It's up to Joe (Schmidt) then if he wants to pick me.
"I got a knee injury last season so I know how much he (O'Brien) will be wanting to get back.
"It's an opportunity for me with Sean out, and I've got that opportunity to play and stake my claim.
"Saying that, there are a few other boys who are probably thinking the same thing."
Henry should square up to one of his Ireland rivals in Friday's league clash, Munster's Tommy O'Donnell, another returning from injury.
Expecting a fierce battle, Henry said: "Tommy is a bit like myself, as he did not get a good run of games until he was a bit older.
"I rate him highly, from training and playing with him on the summer tour (to America), I got to see just how good he is.
"If he is selected and so am I there should be a bit of edge and bit of bite to our contest."
As soon as his hamstring went in that November 9 Test against Samoa, Henry admitted he knew he would be sidelined for some time.
Seven weeks and an ankle knock later, he is relieved to be back.
"I was loving that game to be honest with you, and was getting into the mix, especially in defence," he said.
"I felt my hamstring go and knew my game was up.
"I had my scan on the Sunday, but my bags were packed already.
"I was out for seven weeks, which is the longest I've ever been during a season.
"I had a little setback two weeks ago when I rolled my ankle but I'm back running and am delighted to be back."