Barcelona have revealed Frenkie de Jong and Memphis Depay have picked up hamstring injuries.
The pair were forced off on international duty during Holland's 2-0 win against Poland on Thursday, with De Jong replaced at half-time and Depay limping off seven minutes into the second half.
And the Catalan giants have now confirmed the Dutch duo are set for a spell on the sidelines - joining Ronald Araujo and Jules Kounde - in a big blow to manager Xavi ahead of a busy run of fixtures in October.
A club statement read: 'Tests carried out today have confirmed hamstring injuries for both Frenkie de Jong and Memphis. Midfielder Frenkie de Jong has an elongation of the semitendinosus muscle in his left thigh.
'He is not available for selection and his recovery will dictate his return. Striker Memphis has an injury to the biceps femoris muscle in his left thigh. He is not available for selection and his recovery will dictate his return.'
Both players had returned to Spain after the Poland game and missed their country's 1-0 win against Belgium on Sunday.
The news comes at a bad time, with Barca confirming on Monday that key defender Araujo will undergo thigh surgery in Finland on Wednesday, potentially ruling him out of the World Cup.
The club have not given any indication as to how long Araujo may be sidelined, but it is possible the 23-year-old will remain out of action until 2023.
Versatile French defender Jules Kounde is also currently out of action, picking up a knock in France's 2-0 Nations League win against Austria on Thursday.