The visitors are also looking to end a poor run of form after losing their last three matches across all competitions.
Match preview
Since beating San Jose Earthquakes 2-0 in their first group games of the Leagues Cup, Portland have gone on to lose four straight matches, including two consecutive MLS defeats.
Giovanni Savarese, who spent five years in the Portland dugout, was sacked following a demoralising 5-0 defeat to Houston Dynamo earlier this month, resulting in Miles Joseph being placed in interim charge.
Portland's defensive struggles continued on Saturday when they shipped three more goals in a narrow 3-2 defeat to Vancouver Whitecaps.
The Timbers, who hold the worst defensive record in the Western Conference, have a mountain to climb if they are to finish in the playoffs this season.
With nine matches left to play in the regular season, Portland are currently six points adrift of ninth-placed Austin FC, leaving them at risk of missing the playoffs for the second year in a row.
Despite winning their opening Leagues Cup match, Real Salt Lake were eliminated in the group stage following a heavy 4-0 defeat to Los Angeles FC.
Pablo Mastroeni's side were then knocked out of another cup competition, losing 3-1 after extra time to Houston Dynamo in the semi-finals of the US Open Cup.
Real Salt Lake would have been aiming to get revenge in Saturday's MLS meeting with Houston, but it proved to be another disappointing outing, as they fell to a 3-0 home defeat.
Although they currently have the third-worst defence in the Western Conference, Real Salt Lake sit in fourth place with 37 points to their name.
Impressively, they share the best away record in the MLS with Orlando City, having picked up 21 points from 12 matches, and they will be hopeful of adding to that tally on Wednesday.
Portland Timbers Major League Soccer form:
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Portland Timbers form (all competitions):
Real Salt Lake Major League Soccer form:
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Real Salt Lake form (all competitions):
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Team News
Portland recently confirmed that Jaroslaw Niezgoda suffered an anterior cruciate ligament injury in the defeat to Houston earlier this month.
The hosts are also without the services of David Ayala and Eryk Williamson, who are both ruled out with serious knee injuries.
Defender Dario Zuparic and midfielder Evander are both set to serve one-match suspensions for an accumulation of yellow cards.
As for the visitors, they are unable to call upon Erik Holt and Pablo Ruiz, who are sidelined with shoulder and knee problems respectively.
Goalkeeper Zac MacMath was replaced by Gavin Beavers at the weekend, but the 32-year-old could be recalled for Wednesday's contest.
Braian Ojeda could also return to the starting XI after dropping down to the bench for Saturday's defeat to the Houston Dynamo.
Portland Timbers possible starting lineup:
Bingham; Mosquera, Araujo, McGraw, Bravo; Paredes, D. Chara, Antony; Aprilla, Y. Chara, Mora
Real Salt Lake possible starting lineup:
MacMath; Hidalgo, Glad, Silva, Oviedo; Savarino, Ojeda, Loffelsend, Luna; Arango, Musovski
We say: Portland Timbers 1-2 Real Salt Lake
Both teams will be low on confidence following their recent poor run of results, but Real Salt Lake tend to perform well on their travels, and we think they will get the better of Portland on Wednesday to claim a narrow victory.
How to watch
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