The Toffees will travel across Stanley Park trailing their local rivals by 10 points in the Premier League table, with Liverpool looking to keep themselves in the race for European football.
Six of the previous seven Merseyside derbies in the league have finished as draws, including Brendan Rodgers' last match in charge of the Reds, which finished 1-1 at Goodison Park in October.
Liverpool are undefeated in 10 top-flight derbies, with Everton's last win coming in October 2010 when Tim Cahill and Mikel Arteta netted in a 2-0 triumph at Goodison. The Blues have not won at Anfield since Kevin Campbell scored the winning goal after just four minutes in 1999, when Sander Westerveld, Francis Jeffers and Steven Gerrard were all sent off.
Martinez's semi-final headache
The Merseyside derby is the first fixture Everton supporters look for when the fixture list is announced ahead of the season, but the Toffees can be forgiven for having one eye cast beyond the match against Liverpool. Roberto Martinez's side have an FA Cup semi-final against Manchester United on Saturday to look forward to in what is a defining week for Martinez and his side.
There is added pressure on Everton to claim the bragging rights on Wednesday, especially considering the last time the Toffees were victorious at Anfield was in 1999. Martinez's side then face their biggest game of their season and arguably of Martinez's Everton tenure just three days later. The FA Cup provides the best hope of salvaging something from what has been an underwhelming and frustrating campaign for everyone associated with the club.
Martinez, however, cannot afford to look ahead to the semi-final too much as supporters hate losing to their arch rivals, especially as pressure continues to grow on the Everton boss. But the Toffees were without several first-team players against Southampton on Saturday because of injuries and suspensions and Martinez has a decision to make whether to rest players ahead of the FA Cup semi-final.
Toffees need a much needed boost
Roberto Martinez will be hoping his side can build some momentum ahead of their FA Cup semi-final on Saturday and a win against your local rivals can do just that, but they come into the derby with very little by the way of momentum or optimism.
The Toffees are winless in their last six games and have taken just three points from a possible 18 in that time. All of those points have come in the last three matches, with Everton having been held by Watford, Crystal Palace and Southampton in succession. The latter of those saw the Blues again fail to hang on to a lead, which has been the case in the last three games in which they have opened the scoring.
It is, however, away from home that Everton have been most impressive this season, losing just two of their 16 away league games. However, they have drawn nine of those games and have been forced to share the spoils on a league-high 14 occasions this season.
A win over Liverpool would be a big boost for the Toffees after a frustrating season, especially with an FA Cup semi-final just a few days away, but a defeat will only further dampen the mood on the blue half of Merseyside.
Jurgen Klopp could not have wished for better preparation to his first ever Merseyside derby, with Liverpool going into Wednesday's match after a memorable week. The Reds picked up three wins in the space of seven days last week; back-to-back league victories came either side of their incredible comeback against Borussia Dortmund in the quarter-finals of the Europa League.
The hosts were last beaten a month ago, losing 3-2 away at Southampton. Since then, they have embarked on a five-match unbeaten run in both domestic and European action. A win on Wednesday would propel Liverpool to sixth place, only two points behind Manchester United and six behind Manchester City and Arsenal, who are in third and fourth places.
Romelu Lukaku and Ross Barkley are likely to be recalled after being named as substitutes against Southampton on Saturday, while James McCarthy returns from his suspension. Seamus Coleman and Phil Jagielka are both absent, however, with hamstring injuries.
Liverpool could be without Divock Origi and Kolo Toure, who suffered respective back and hamstring injuries against Bournemouth on Sunday, while Emre Can and Jordan Henderson are not expected to play again this season.