Everton left-back Leighton Baines will be out for at least three months after having ankle surgery.
The 30-year-old was injured in training before the season started after returning from an operation on the same ankle.
The England international missed the final two games of last season.
Boss Roberto Martinez said he had a "perfect" pre-season and described the injury as a "disaster".
The club said on Thursday that Baines had "undergone a successful ankle operation" and is set to miss "the next 12 to 14 weeks".
Baines could now miss more than a dozen Premier League matches including the Merseyside derby against Liverpool, as well as five England games.
Roy Hodgson's side face San Marino, Switzerland, Estonia and Lithuania in September and October as part of their Euro 2016 qualifying campaign, plus a friendly against France in November.