Arsenal midfielder Santi Cazorla has been ruled out for three months after learning he will require surgery on an ankle injury.
The Spaniard has not featured since and now faces an extended spell on the sidelines because his rehabilitation has not progressed as hoped.
The blow comes less than 24 hours after Arsene Wenger insisted Cazorla's return was being delayed only by inflammation, adding that he had suffered "no setback".
Cazorla, who missed nearly five months of action with successive knee and Achilles injuries last season, will travel to Sweden early next week for the procedure.
After a run of seven consecutive victories ending in the thrashing of Ludogorets, Arsenal have won four, drawn four and lost one in all competitions since Cazorla's injury.
Last week, Wenger explained the importance of Cazorla - who has become Arsenal's first-choice central midfielder after joining the club as an attacking midfielder or winger - to the way his side functions.
"Santi is important to our technical stability in the team, to the quality of our decision-making and to our build-up from deep midfield to the high midfield," the Frenchman told reporters.
"That is an important stage because it gets the ball out from the defenders. Santi is a massive player for us.
"But we have enough quality players in our side to get around that. We are good enough to find solutions despite the fact he is not there."