The hosts currently sit in the relegation playoff place, three points adrift of automatic safety, while their opponents sit just five points ahead in 13th place.
Maritimo suffered a disappointing defeat last out, as they travelled to take on Belenenses.
Before that, Julio Velazquez recorded his second victory as Maritimo manager, as his side won a crucial game against fellow strugglers SC Farense.
Ali Alipour netted the only goal of the game on the stroke of half time to secure a vital win and see Os Verde-Rubros leapfrog Farense to move out of the automatic drop zone, jumping up to 16th spot.
Velazquez was brought into the club to replace Milton Mendes in March with the side sat bottom of the table, and he has started their rise with two wins from their first five games.
He will look to make a return to winning ways on Wednesday, to continue his side's rise up the table and further boost their survival hopes with what would be a crucial result over one of their rivals in the battle to avoid the drop.
They take on a Rio Ave side who have been dragged into the relegation scrap, having failed to win any of their last five games.
Rio Ave picked up an impressive result last time out, holding Braga to a 0-0 draw despite forward Gelson Dala being shown a red card with 10 minutes to go.
While that seems very positive at first glance, the result did stretch Os Rioavistas' winless run to five games, which has seen them fall to 13th place in the top flight.
Miguel Cardoso's side now sit just five points ahead of Wednesday's opponents, and seven points above the automatic drop zone.
That means they could quickly find themselves falling into the bottom three if results continue to go against them, with every side below them battling hard to avoid the drop.
Their struggles this season have come in attack, with only Belenenses scoring fewer than the 22 goals that Os Rioavistas have netted in 27 Primeira Liga matches this campaign.
Cardoso's men will now be desperate to put an end to their poor run on Wednesday, in order to increase that gap between themselves and the bottom three.
Maritimo will be without left-back Marcelo Hermes, who will serve a suspension after he picked up his fifth yellow card of the season last time out.
Centre-back Leo Andrade will also continue his spell on the sidelines, having missed the Belenenses match through injury.
However, they will welcome Zainadine Junior back into the defence, after he served a suspension last time out.
They could be also hugely boosted by the return of talisman Rodrigo Pinho to the starting side, after the striker came off the bench last time out following a spell out through injury.
Rio Ave forward Gelson Dala will be absent for this game, after he was shown a red card in the draw with Braga.
Maritimo possible starting lineup:
Abedzadeh; Junior, Africo, Rene; Winck, Jean, Bambock, Costa, China; Pinho, Tagueu
Rio Ave possible starting lineup:
Kieszek; Pinto, Borevkovic, Santos, Coentrao; Tarantini, Pele; Mane, Guga, Geraldes; Ronan
We say: Maritimo 2-1 Rio Ave
Despite the defeat last time out, Maritimo seem slightly revitalised under Velazquez and have stepped up in crucial games on two separate occasions.
We see them, boosted by the return of Pinho, stepping up again as they take on a struggling Rio Ave side who have several important players missing from the squad.