The winger, who arrived at Molineux last summer from Valencia for £27.5 million, made just 13 Premier League appearances in the first half of the campaign before being loaned out to Benfica.
However, his spell in Portugal has been injury hit, and after undergoing a knee operation in March that kept him out for around a month, he is now set for more time on the sidelines.
Benfica have confirmed Guedes has suffered a cartilage injury to his left knee and said in a statement: "The advanced needs surgical treatment, to be carried out in the next few days.
Guedes has made a total of 13 appearances for Benfica - who go into the final game of their league campaign favourites to win the title
Back in March, the Express & Star reported that Wolves are likely to try and offload the big money signing in the summer.
Once Julen Lopetegui arrived at the club, Guedes was left out of the squad for two consecutive games before completing his loan move to Portugal.
In March, reports in Portugal suggested that Benfica are keen to keep the player next season, however a second knee surgery in three months may play a part in any move.