The Paraguay international is recovering from a knee operation and is expected to be out until September as City's big money signings struggle for fitness ahead of Saturday's game.
Hughes has spent almost £100million on big-name signings during the summer and his team will be under intense pressure to deliver when they travel to his former club.
DebutsOf the major new signings, Kolo Toure, Gareth Barry and Carlos Tevez could all make their debuts at Ewood Park.
Emmanuel Adebayor, a £25million signing from Arsenal, faces a race against time to make his debut after returning from international duty for Togo with a slight groin injury.
Fellow £25million man Carlos Tevez is in contention to make his debut after overcoming a minor heel problem while Craig Bellamy has overcome the knee injury which kept him out of the Wales squad in midweek.
Meanwhile, Belgian international Vincent Kompany is still sidelined with a toe injury while midfielder Michael Johnson will need another two weeks to recover from an abdomen injury.
BlackburnBlackburn boss Sam Allardyce's main concern heading into the match is the availability of captain Ryan Nelson who is struggling with a knee injury sustained in the 2-0 defeat to Dundee United last Saturday.
Australian midfielder Vince Grella and defender Chris Samba are both fit and are expected to start as Rovers look to dent City's title credentials early on.
New signing Nikola Kalinic is still waiting for a work permit therefore South African striker Benni McCarthy looks likely to start in attack.
Possible starting XIsBlackburn: Robinson, Jacobsen, Warnock, Nelsen, Samba, Pedersen, Emerton, Andrews, Grella, Diouf, McCarthy
Man City: Given, Richards, Dunne, Toure, Bridge; Wright-Phillips, Barry, Ireland, Bellamy; Robinho, Tevez