American left back Sam Vines injured a leg and needed surgery, eliminating him from consideration for the United States World Cup roster.
Right back Sergino Dest missed his second straight match for AC Milan with what the club called adductor fatigue earlier in the week.
- Stream on ESPN+: LaLiga, Bundesliga, MLS, more (U.S.)
- 2022 World Cup: All confirmed squad lists for Qatar
Forward Josh Sargent and defender Cameron Carter-Vickers returned to their club starting lineups on Saturday, the last weekend of matches before U.S. coach Gregg Berhalter announces his roster.
A 23-year-old from Colorado, Vines had ankle surgery at AZ Monica Deurne hospital in Antwerp, Belgium, Vines' club, Royal Antwerp, announced Saturday.
Vines said he broke his tibia and will be sidelined for three to four months.
"Life is full of ups and downs. Unfortunately yesterday I broke my tibia and had to get surgery," he wrote on Instagram.
"Upset I missed the chance to be in the World Cup but I will be supporting the boys until the end."
Vines last played on Oct. 30 against Charleroi. He has nine international appearances and was considered a possibility for the U.S. roster as a backup to starting left back Antonee Robinson.
Loaned to Milan from Barcelona, the 22-year-old Dest has been limited to two starts and six substitute appearances this season. He is the Americans' first-choice right back and a backup to Robinson at left back.
Sargent, a 22-year-old from O'Fallon, Missouri, started for Norwich at Rotherham in England's second-tier Championship after missing a pair of games with a calf injury sustained against Burnley on Oct. 25. Sargent has eight goals for Norwich this season.
Carter-Vickers, a 24-year-old son of former NBA player Howard Carter, started for Celtic against visiting Dundee United in the Scottish Premier League. He missed a Champions League match at Real Madrid on Wednesday because of soreness after playing 90 minutes during last weekend's game at Livingston, which has an artificial turf surface.
Berhalter is to announce his 26-man roster Wednesday, ahead of FIFA's Nov. 14 deadline.
Back in the World Cup after missing the 2018 tournament, the U.S. opens against Wales on Nov. 21, plays England in a Black Friday matchup four days later and closes group play on Nov. 29 against Iran.