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Crystal Palace forward Eberechi Eze and midfielder Adam Wharton are both set to be out for a month with their injuries, says manager Oliver Glasner.
Both players went off during the Eagles' midweek Carabao Cup last-16 win against Aston Villa.
Wharton is to undergo surgery for a groin issue while forward Eberechi Eze is out with a hamstring injury.
"It will be very ambitious to have [Eze] back after the [mid-November] international break, but I know we have a great medical department and he will work quite hard, so let's see," said Glasner.
"We took the final decision [on Wharton], he will have surgery. He tried [training] but the pain is too much and then it makes no sense. He has really struggled in the last weeks and months.
"So now we took the decision to have the surgery, and we hope to have him back after maybe four weeks."
Palace, who secured their first Premier League win of the season by beating Tottenham 1-0 last weekend, are away at fellow strugglers Wolves on Saturday.
They will also be without Colombian midfielder Jefferson Lerma until at least the international break, which starts on 11 November, because of a hamstring issue.
Glasner added: "Many managers are talking about the same issues, and especially when we look at our injured players - all who played a long tournament in the summer, having no holidays, having no pre-season and then many, many games.
"There is a moment when you have to pay the bill, and we had to pay it the last one, two, three weeks, but it is how it is and we are still a strong squad."