The Egyptian superstar, a key pillar of Liverpool's run to Kiev, was the subject of a rough challenge from Sergio Ramos and stayed down for some time before walking off with the club physios.
Salah landed awkwardly on his shoulder after a challenge from Sergio Ramos.
Ramos appeared to keep hold of Salah's arm as they tumbled to the ground and the Reds forward appeared to be in some discomfort and lay motionless on the pitch with his left arm outstretched.
He came back on the field and tried desperately to continue playing but when he collapsed again, he knew the game was up.
Jurgen Klopp turned to Adam Lallana as his replacement.
Salah was visibly distressed, leaving the field and walking down the tunnel with tears streaming down his face.
When Liverpool last won the Champions League in 2005, Harry Kewell was taken off with an injury but his replacement, Vladimir Smicer, played a crucial part in their eventual victory.
Real Madrid were also struck down by an injury in the first half in Kiev, with Dani Carvajal leaving the pitch in tears after appearing to damage his hamstring in a non-contact incident.