Wolves say Portugal forward Pedro Neto will miss the 2022 World Cup as he requires an ankle operation.
The 22-year-old suffered the injury in their 2-0 defeat by West Ham last Saturday, 1 October, when he was substituted after 24 minutes.
The Premier League club said that Neto strained his lateral ligaments.
"Following further evaluation and a specialist opinion this week, it is planned for him to undergo surgery," a club statement added.
"This means that, unfortunately, he will not be fit for the upcoming World Cup."
Neto has made three appearances for Portugal and, while he was in their squad for recent Nations League games against the Czech Republic and Spain, he did not play in either.
The World Cup will take place from 20 November to 18 December in Qatar.
Wanderers are without a manager following Sunday's sacking of Bruno Lage and Neto's absence further diminishes their already-depleted attacking options.
Raul Jimenez and Hwang Hee-chan are both sidelined with groin problems while summer signing Sasa Kalajdzic suffered a potentially season-ending knee injury on his debut.
Recent free-transfer signing Diego Costa and Goncalo Guedes, without a goal in eight games since a £27.5m summer move from Valencia, are their only recognised fit senior strikers.