The 26-year-old was initially called up to represent the Samurai Blue in AFC World Cup qualifiers against Myanmar on Thursday and Saudi Arabia next Tuesday.
However, Mitoma has released a joint statement with the Japan Football Association revealing that he has regrettably decided to pull out of the national team squad to concentrate on his recovery from an unspecified injury.
"Since this is a World Cup qualifier, I joined the team believing in my potential to contribute," the statement read as quoted by The Athletic.
"But unfortunately, seeing as I won't be able to play at 100 per cent, I've decided to let my teammates play on my behalf, as much as I regret doing so.
"For now, I will work hard on recovering as soon as possible."
Mitoma has developed into a star player for Roberto De Zerbi's side over the last 12 months, contributing with 13 goals and 12 assists in 58 appearances across all competitions.
However, the 18-cap Japan international has emerged as doubt for Brighton's next Premier League fixture away against Nottingham Forest on November 25.
Mitoma is the ninth player to be added to Brighton's growing injury list, with the Seagulls missing eight players for the 1-1 draw with Sheffield United last weekend.
Evan Ferguson was a notable absentee from the clash with the Blades due to a knee problem and he has since emerged as a doubt for the Republic of Ireland's Euro 2024 qualifier against the Netherlands on Friday.
However, Ireland manager Stephen Kenny has revealed that the 19-year-old striker is "determined" to play against the Dutch, suggesting that the issue is not a serious one.
Captain Lewis Dunk, James Milner, Pervis Estupinan and Tariq Lamptey are also nursing injuries, but De Zerbi is hopeful that the quartet, along with Ferguson, can return after the international break.
"We lost Evan but in Amsterdam (against Ajax) he was not in perfect condition," De Zerbi told reporters as quoted by The Argus. "I don't know the time but I hope to find the injured players - Evan, Tariq Lamptey, Estupinan and Lewis Dunk - after the break.
"When we start the training, I hope and I think we can find them on the pitch."
Meanwhile, Solly March, Danny Welbeck and Julio Enciso remain longer-term absentees for the Seagulls, while Jakub Moder is closing in on a return following a 19-month layoff with a troublesome knee problem.
Away from the injury front, Brighton will have to cope without midfielder Mahmoud Dahoud for their next three matches after he was shown a straight red card for a late tackle in the draw with Sheffield United.
Brighton, who have failed to win any of their last six Premier League games, currently sit eighth in the table, six points behind Aston Villa in fifth and seven behind Tottenham Hotspur in fourth.