The announcement came late on Tuesday night following tests conducted on the squad.
The affected players have not been named but they have been placed in quarantine.
Espanyol becomes the second La Liga club to announce some of its players and staff have contracted the virus.
Valencia confirmed on Sunday that 35 percent of the club’s staff including players Ezequiel Garay and Eliaquim Mangala had tested positive for Covid-19.
"This afternoon it was confirmed that 6 members from the first squad and the coaching staff of RCD Espanyol of Barcelona have tested positive in COVID-19 tests carried out in the last few hours,” Espanyol’s club statement read.
“All are found to have mild symptoms and are complying with medical recommendations.”
Spain is the second worst European country affected by the Coronavirus pandemic after Italy, having recorded 11,748 cases and 533 deaths.
The Spanish top flight has been suspended for two match days but with the virus showing no signs of slowing down, the halt could be extended further.
Espanyol are bottom of the league table with 20 points and just four wins all season.
On Tuesday, UEFA announced the postponement of this summer’s European championships to 2021 while the 2020 Copa America has also been pushed back a year because of the Coronavirus.