Real Madrid face a defensive crisis ahead of huge clashes against Bayern Munich and Barcelona after Pepe suffered a double rib fracture in Saturday's 1-1 draw with Atletico Madrid.
Pepe opened the scoring with a towering header seven minutes into the second half but then had to be replaced after clashing with teammate Toni Kroos.
"He has been diagnosed with a fracture in the seventh and eighth left ribs," Madrid said in a statement.
The Portuguese defender is expected to be sidelined for up to a month.
Madrid are already set to miss central defender Raphael Varane for the rest of the month due to a hamstring injury.
The European champions face Bayern in the first leg of their Champions League quarter-final on Wednesday.
Bayern then travel to the Spanish capital for the second leg on April 18 before Real host Barca in a potential La Liga title decider on April 23.