The sides have had mixed starts to the new campaign, with the hosts currently 11 points and seven places above the visiting team.
Orlando City failed to win away from home for the third match on the bounce as they were annihilated 5-0 by New York City FC on Friday.
The Lions fielded a relatively weaker starting XI for the contest and were made to pay by a rampant opposing side who were in no mood to let them off.
Nonetheless, Saturday's hosts remain well-placed on the log with a tally of 25 points from 15 outings, which leaves them third in the Eastern Conference.
Next up is a clash against an Atlanta United side against whom they are unbeaten in the last six encounters involving the teams.
Atlanta United's wait for a third league win of the campaign goes on for the 10th consecutive game following a 1-0 loss to Columbus Crew on Saturday.
Jonathan Mensah came up with the game's only goal 20 minutes into the second period to secure a hard-fought victory for his side.
Away matches have proven to be a major Achilles heel for Rob Valentino's troops so far, with their eight outings yielding only five points and no wins.
The Five Stripes head into this weekend's tie eight points away from the last playoff place as the season approaches its midway point, and their performances on the road need to improve if they are to avoid missing out on the post season for the second consecutive year.
Brazilian defender Ruan made his return to action in the defeat to New York City FC following a 10-game layoff due to an abdominal strain.
Meanwhile, Alexandre Pato remains sidelined with a knee problem, which he sustained on his debut for the home side in April.
Emerson Hyndman and Franco Ibarra are major doubts for the contest as they continue to nurse hamstring and muscle injuries respectively.
Ezequiel Barco is with the Argentina national team at the Olympics in Tokyo, while the trio of Brad Guzan, George Bello and Miles Robinson are on duty with the United States at the Gold Cup.
A knee injury will rule Mohammed Adams out for a fourth consecutive game, denying him an opportunity to add to his three appearances this term.
Orlando City possible starting lineup:
Gallese; Moutinho, Smith, Schlegel, Jansson; Perea, Rosell, Pereyra; Mueller, Michel, Nani
Atlanta United possible starting lineup:
Kann; Lennon, Franco, Walkes, Hernandez; Rosseto, Sosa, Moreno; Martinez, Chol, Mulraney
We say: Orlando City 2-1 Atlanta United
The home side will be expected to claim all three points against their struggling visitors, who have not fared well on the road this term. We anticipate a keenly contested affair, with the hosts just edging it by a narrow margin at the sound of the final whistle.