FRF, which did not specify the nature of the 28-year-old left back's injury, said in a statement that Sepsi returned to his club FC Nurnberg for treatment after failing to recover for the much-anticipated match in Cluj-Napoca.
Romania, who beat Lithuania 1-0 in a friendly on Wednesday to extend their unbeaten run to 16 games, have been drawn in European Championship Group A with hosts France, Switzerland and Albania.
Spain, who on Thursday drew 1-1 in Italy to end a run of seven successive wins, are in Group D alongside Turkey, Croatia and the Czech Republic.
(Reporting by Angel Krasimirov, editing by Ed Osmond)
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