"Lewandowski picked up an injury in the recent game against Villarreal. Tests have diagnosed a fracture of the left eye socket," said Barcelona in a statement.
"He will miss the game against Atletico Madrid."
Copa del Rey holders Barcelona suffered a 4-0 defeat in the first leg against Diego Simeone's side at the start of February.
Lewandowski, 37, has played a bit-part role for Barca this season, often left on the bench in favour of Ferran Torres.
On as a substitute, the former Bayern Munich striker netted LaLiga leaders Barca's fourth goal in the 4-1 win over Villarreal on Saturday.