Midfielder Roman Zobnin became the fifth Russian player to be ruled out of the Confederations Cup because of injury on Tuesday.
The Russian Football Union said Zobnin damaged cruciate and lateral ligaments in his right knee during Monday's 3-0 friendly win over Hungary. The RFU said he was heading to Rome for treatment and "will not take part in the Confederations Cup."
The 23-year-old Zobnin has started Russia's last seven games and was a key player in Spartak Moscow's run to the Russian league title this season.
Russian national team doctor Eduard Bezuglov said Zobnin would be out for at least four months, according to Russian media.
Out of their original 30-man provisional squad, Russia have also lost midfielder Alan Dzagoev, forward Artyom Dzyuba, naturalized Brazilian right back Mario Fernandes and goalkeeper Andrei Lunyov to various injuries.
Russia starts their Confederations Cup campaign in St. Petersburg against New Zealand on June 17, followed by group games against Portugal and Mexico.
Meanwhile, Zobnin's club manager Massimo Carrera extended his contract as coach of Spartak on Tuesday, signing a new two-year deal through the end of the 2018-19 season. His previous contract had one season remaining.