The Belgium international has missed much of the season with knee injuries but has recently been struggling with a hamstring problem.
Man City injuries
Fernandinho will miss Sunday's game after suffering a knee problem during the game with Manchester United at the end of April.
De Bruyne injured his hamstring against Tottenham last month but could be part of the squad this weekend.
Benjamin Mendy is ruled out with a knee problem.
Man City suspensions
Neither side have any suspensions.
Man City potential starting line-up
The main selection dilemma heading into Sunday's game, if De Bruyne is not fit enough to start, will be whether to restore Leroy Sane to the line-up or stick with Phil Foden in midfield.
Sane dropped to the bench against Leicester on Monday after a disappointing display against Burnley, but he replaced Foden in the second half after the youngster failed to make a mark on the game. The Germany winger, however, enraged Pep Guardiola at times during his appearance and it leaves the Catalan with a tough decision to make.
Otherwise, most of the team picks itself. Ederson, Kyle Walker, Aymeric Laporte, Oleksandr Zinchenko, David Silva, Bernardo Silva, Raheem Sterling and Sergio Aguero are sure to start, barring any surprise fitness issues over the weekend.
Vincent Kompany has started City's past four matches and is likely to do so again, especially given his match-winning contribution on Monday.
Brighton team news
Jose Izquierdo (knee) and Davy Propper (hamstring) are doubts for Brighton.
Opta match facts
- A win will guarantee Manchester City their fourth Premier League title, and sixth overall in the English top-flight. They would be the first team to retain the crown since Manchester United in 2008-09.
- The last team to be top going into the final day of an English top-flight season and not win the title were Liverpool in 1988-89.
- Manchester City have won their last four meetings with Brighton in all competitions, already beating the Seagulls twice this season (once in the league, once in the FA Cup).
- Brighton have lost their last three final games of a top-flight season, losing 0-4 at Liverpool last term.
- Brighton and Hove Albion have played more top-flight matches against reigning champions without winning than any other team in top-flight history (11 – W0 D2 L9).
- Brighton manager Chris Hughton has lost eight of his 10 matches against Man City in all competitions (W1 D1), though his only victory came in a match on the closing day of the season (3-2 with Norwich in 2012-13).
TV coverage & kick-off time
Kick off is 3pm BST (10am ET) on Sunday and will be shown on Sky Sports Main Event in the United Kingdom. It will be shown on NBC in the United States, and on various channels around the world.