Steve Corica's side are 10 points clear at the top of the table with two games in hand on second-placed Melbourne City but have lost both of their meetings with Wanderers this season and will be keen to exact revenge.
Wanderers are enduring a sub-par season, with just seven wins from their 20 games so far and sitting eighth in the A-League standings, above only Newcastle Jets, Melbourne Victory and Central Coast Mariners.
However, their recent form has been more positive, with just one defeat in their last six league games, including a run of three wins in four outings.
Despite this upsurge in results, Wanderers find themselves 22 points adrift of their local rivals, despite having played an extra game.
Sydney FC have won 15 and lost just two of their 19 A-League games so far this season and look set to run away with the title.
However, both of their two losses have been 1-0 defeats suffered at the hands of local rivals Wanderers, and Corica's men will be keen to avoid a third straight derby defeat.
The league leaders have the best defensive record in the division and are the only side to have conceded fewer than 20 so far, allowing only 15 goals for their opponents.
Corcia's side have been equally efficient at the other end, netting 41 times so far in the league - four clear of the next best side.
Their most recent derby defeat ended a run of six straight league wins, and a 0-0 draw against Perth Glory last time out will not be deemed good enough for a title-chasing side that has become used to higher standards and will be keen to return to winning ways.
Western Sydney Wanderers A-League form: WDWWLD
Sydney FC A-League form: WWWLWD
Sydney FC form (all competitions): LWLDWD
Caretaker Wanderers boss Jean-Paul de Marigny - who replaced Markus Babbel in January - has only long-term absentees to deal with.
For Sydney FC head coach Corica, however, there are no injuries to contend with, boasting fully-fit squad to choose from as he seeks to win the Sydney derby at the third time of asking this season.
Western Sydney Wanderers possible starting lineup:
Lopar; Mourdoukoutas, McGowan, Jurman; Russell, Schwegler, O'Doherty, Carluccio; Muller; Duke, Cox
Sydney FC possible starting lineup:
Redmayne; Grant, McGowan, Wilkinson, King; Caceres, Brattan, Retre, Ninkovic; Barbarouses, Le Fondre
We say: Western Sydney Wanderers 1-1 Sydney FC
Sydney FC may be flying high at the top of the table, but Western Sydney Wanderers seem to have their number this season. The league leaders may be motivated enough to avoid a third successive derby defeat, but they could be held to their third draw of the campaign.