Mkhitaryan has previously missed a group game at Azerbaijan this season.
Henrikh Mkhitaryan will not play for Arsenal in the Europa League final against Chelsea next week because of concerns about political tension between his native Armenia and Azerbaijan, which is hosting the game.
Arsenal said on Tuesday it reached the decision following discussions with the midfielder and his family and after "thoroughly" exploring all the options available.
"We have collectively agreed he will not be in our travelling party," Arsenal said in a statement, adding that it has "written to UEFA expressing our deep concerns about this situation."
Mkhitaryan said on Instagram it had been a "tough decision" to pull out of the game, adding: "I must admit, it hurts me a lot to miss it."
He has missed previous group games in Azerbaijan for both Arsenal and former club Borussia Dortmund.
"Micki has been a key player in our run to the final," Arsenal said, "so this is a big loss for us from a team perspective."
The Azerbaijan government previously said it would allow Mkhitaryan to play in the final in Baku on May 29. UEFA had also said it would ensure Mkhitaryan's safety.
"Working alongside Arsenal FC, UEFA sought and received assurances regarding the player's safety in Azerbaijan from the highest authorities in the country," European soccer's governing body said in an emailed statement.
"As a result of these guarantees, a comprehensive security plan was developed and given to the club. While the club acknowledges the efforts that UEFA and the Azeri government have gone to in this matter, we respect the personal decision not to travel with the player."
Nagorno-Karabakh is a region of Azerbaijan which has been under the control of ethnic Armenian forces backed by Armenia since a war there ended in 1994. Some neighboring districts are also under the control of those ethnic Armenian forces. International efforts to settle the conflict have stalled.
"We at all times put the sport as something very separate from these political issues and of course the same issue is again with Mkhitaryan," Azerbaijan Sports Minister Azad Rahimov said last week.
Tensions between Azerbaijan and Armenia have spilled into European soccer tournaments since the neighbouring nations were drawn together in a qualifying group for the 2008 European Championship.
Both games were eventually cancelled, after Azerbaijan refused to host Armenia and no agreement could be reached on neutral venues.
UEFA has since separated the countries in its competition draws ensuring that their national and club teams do not play each other.
Arsenal will be playing its first European final in 13 years and looking to win its first continental trophy since the 1994 European Cup Winners' Cup. The game has even greater importance because Arsenal needs to win to secure qualification to the Champions League after missing out on a top-four finish in the Premier League.
"We're also very sad," Arsenal said, "that a player will miss out on a major European final in circumstances such as this, as it is something that comes along very rarely in a footballer's career."
Arsenal also has been critical of the choice of Baku as host of the final after receiving only 6,000 tickets by UEFA and because of the "extreme" problems fans face to get to the match.
There are relatively few flights to Baku from Western Europe, though more are being operated for the final, and prices are far above usual levels.
Arsenal's then-chief executive, Ivan Gazidis, was on the UEFA executive committee when Baku was chosen as Europa League host in September 2017. Mkhitaryan was then with Manchester United, playing in the Champions League, and joined Arsenal the following January.
Baku won the Europa League final hosting rights in a bidding contest that originally included Seville, Spain, and Istanbul. Seville was excluded because Madrid was awarded the Champions League final, which will be played on June 1.
UEFA evaluated each bidder, though a subsequent report did not mention the Armenia issue in a section analyzing security issues for Baku.
