In contrast to their hosts, the Lions will carry significant momentum into the midweek contest after recording three successive victories.
Match preview
Having won six, drawn eight and lost nine of their 23 matches, Nashville are currently sitting in ninth position in the Eastern Conference, with only goal difference keeping them above Montreal.
Nashville are enduring a poor run of results, having lost each of their last four matches to Inter Miami, Columbus Crew, Portland Timbers and DC United.
They would have been particularly disappointed to lose 2-1 in Saturday's away game against DC United after they took the lead through Tyler Boyd's 19th-minute opener.
Nashville may have conceded 10 goals across their last four matches, but is at the opposite end of the pitch where they have struggled throughout the campaign, having netted just 26 goals in 23 games - only the New England Revolution have scored fewer in the MLS this season.
After playing three consecutive away games, they will hope a return to GEODIS Park can spark an upturn in fortunes, even though they have won just one of their previous four home matches.
Orlando are sitting in seventh position and four points above Wednesday's opponents after putting together a fine run of form.
The Lions have won four of their last five matches, including victories in their last three outings against Toronto, DC United and New England.
They showed great fight to come from a goal down in Saturday's away game against the Revolution, with Facundo Torres scoring either side of a Ramiro Enrique effort to guide Orlando to a 3-1 victory.
Having won back-to-back away games, Orlando have now taken 18 points from their 12 MLS road trips this season, giving them the fourth-best away record in the Eastern Conference.
They may fancy their chances of claiming three more points on Wednesday after winning each of their previous three games against Nashville via a 1-0 scoreline, including their last two trips to GEODIS Park.
Nashville SC Major League Soccer form:
W
W
L
L
L
L
Orlando City Major League Soccer form:
D
W
L
W
W
W
Team News
Nashville are unable to call upon Julian Gaines and Lukas MacNaughton due to ankle injuries, while Anibal Godoy and Randall Leal are ruled out with thigh and hip issues respectively.
The hosts are also having to cope without the services of their captain Walker Zimmerman, who has been named in the USA squad for the upcoming Olympics in France.
In Zimmerman's absence, Bauer started in central defence at the weekend, and he is set to retain his spot alongside Jack Maher in the centre of the Nashville backline.
Meanwhile, the visitors remain without goalkeeper Mason Stajduhar and defender Michael Halliday due to leg and knee injuries respectively.
Enrique is set to start a second successive game in the absence of Duncan McGuire, who has been selected to represent the USA at the Olympic games.
Uruguayan winger Facundo Torres will be looking to continue his fine form after scoring seven goals in his last nine MLS appearances.
Nashville SC possible starting lineup:
Willis; Moore, Bauer, Maher, Lovitz; Davis, Yearwood; Boyd, Mukhtar, Surridge; Bunbury
Orlando City possible starting lineup:
Gallese; Thorhallsson, Schlegel, Jansson, Santos; Araujo, Cartagena; Torres, Ojeda, Angulo; Enrique
We say: Nashville SC 1-3 Orlando City
Nashville will be low on confidence after four straight defeats, while their opponents will be full of belief following three consecutive victories, and we think Orlando will continue to build momentum by claiming another victory in Wednesday's away fixture.