Atletico Madrid captain Koke is set to miss the Champions League last-16 first leg against Manchester United on Wednesday after the club said he has a thigh injury.

Koke's absence would be a blow for Atletico, who already have concerns about the fitness of central defender Jose Gimenez, taken off at halftime against Osasuna on Saturday.

"Our player Koke finished the last game against Osasuna with discomfort," an Atletico statement on Tuesday read.

"The midfielder has undergone medical tests in the last few days, the results of which have shown that he is suffering from a thigh muscle injury."

With Thomas Lemar out injured, Atletico could field Marcos Llorente, Geoffrey Kondogbia and Hector Herrera in a midfield three.

Yannick Carrasco is suspended while Daniel Wass and Matheus Cunha are also injured. (AFP)