Japan winger Kaoru Mitoma hurt his right foot and left the stadium on crutches after playing the second half of Brighton's 2-0 defeat at Brentford on Friday in the English Premier League.
With just over five weeks to the start of the World Cup in Qatar, the injury could be a devastating blow to both Mitoma and Japan after the 25-year-old made crucial contributions to Hajime Moriyasu's side over the past year.
Trailing 1-0 at Gtech Community Stadium, Brighton's new manager Roberto De Zerbi sent on Mitoma at halftime down the right instead of his usual left. The player hurt his leg just two minutes in following contact with an opposition player while looking to enter the box.
Mitoma showed signs of discomfort but carried on and provided a fine cross with the injured foot in the 68th minute, only to see a free header from Solly March saved by David Raya.
Mitoma switched to left for the last 15 minutes but Brighton recorded their first back-to-back defeats of the season after Ivan Toney flicked in a clever 27th-minute opener before scoring a 64th-minute penalty.
Japan clinched their World Cup qualification in March away to Australia when late substitute Mitoma hit a brace in a 2-0 win. He also scored in Japan's 2-0 friendly win over the United States on Sept. 23.
In Germany, defender Maya Yoshida played the full 90 minutes but Schalke lost 3-0 at home to Hoffenheim for their fourth straight defeat in the Bundesliga.