Messi was denied by goalkeeper Diego Lopez in the 62nd moment after a foul on Sergi Roberto.
Espanyol's Oscar Melendo at that point opened home with two minutes left in the wake of hustling onto Marc Navarro's cross.
The second leg happens at the Nou Camp on Thursday, 25 January.
In the other quarter-last ties, Diego Costa scored his third objective in four recreations amid Atletico Madrid's 2-1 crush at home by Sevilla.
Costa put Atletico ahead in the 73rd moment just for goalkeeper Miguel Angel Moya to mysteriously push a theoretical check that diverted off protector Lucas Hernandez into his own particular net.
New Sevilla mentor Vincenzo Montella at that point fixed his third win since landing in Spain as Joaquin Correa hustled on to Wissam Ben Yedder's go before completing with two minutes remaining.
Goncalo Guedes and Rodrigo scored in the second half as Valencia dug out from a deficit to record a 2-1 prevail upon La Liga strugglers Alaves.
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