It's 34 years since the Seagulls were in the top flight and they couldn't have been handed a tougher test on the opening weekend, with City winning more league games away from home (12) than any other Premier League team last season.
Brighton, who have only won one of their last five opening games of the season, are set to hand Anthony Knockaert a late fitness test. The former Leicester man, who claimed 15 goals in the Championship last season, injured ankle ligaments in July but is close to making a return.
Four of Brighton's summer signings are expected to feature - Mat Ryan, Markus Suttner, Davy Propper and Pascal Gross - but Chris Hughton is without injured pair Sam Baldock and Beram Kayal.
Meanwhile, City have spent over £200million on new signings this summer and at least three new faces are expected to start on Saturday. Ederson is likely to start between the posts, while Kyle Walker and Danilo are also in the frame.
Benjamin Mendy, a summer capture from Monaco, is missing due to a thigh injury and Bernardo Silva could miss the opener having recently returned to training after playing for Portugal at the Confederations Cup.