The expansion side earned a maiden road point last week with a goalless draw in Colorado to sit seventh in the Eastern Conference standings.
Antonio Carlos has been ruled out with a left hamstring injury that will force him to miss three to four months.
Michael Halliday is a doubt as the 19-year old, who has yet to feature this season, nurses a left thigh injury.
Vinicius Mello continues to recover from surgery on his left foot. Chris Hegardt also remains out with a knee issue. Yordy Reyna (lower leg injury), Adan Armour (left leg injury), and Joseph Mora (health & safety protocols) are also listed as out.
Kamil Jozwiak is doubtful after picking up an illness during the week. Adam Armour (knee) and Yordy Reyna (lower leg) are also considered doubts.
Orlando City: Gallese; Moutinho, Schlegel, Jansson, Ruan; Araujo, Urso; Torres, Pereyra, Pato; Kara
Charlotte FC: Kahlina; Mora, Corujo, Fuchs, Lindsey; Alcívar, Bronico, Franco; Ortíz; Ríos, Swiderski
Ones to watch
Ercan Kara (Orlando City)
Brought in from Austrian side Rapid Wien, he has provided the Lions with a real threat up front, acclimating quickly to life in the MLS, scoring four goals and will look for his first at home.
Karol Swiderski (Charlotte FC)
He's been everything Charlotte envisioned he would be when they made him one of their two Designated Players, scoring four goals and recording an assist.
The Pole leads the club in shot attempts with 21 and shots on target with 13. He's also proven to be a threat anywhere on the field, scoring twice inside the box and twice outside of the box.
This is the first-ever matchup between Orlando City and Charlotte.
The match will be streamed nationally on ESPN+. In Orlando, Fox 35 Plus will have all of the action while WAXN will have English-language coverage in Charlotte. Telemundo Charlotte will carry the Spanish-language broadcast.
Kickoff is set for 7:30pm Eastern time.