The 60-year-old Mattingly experienced mild symptoms when he arrived at the park for the game. The former Yankees star was vaccinated in mid-April.
Mattingly's case is isolated, the team said. The remainder of the coaching staff and players underwent rapid antigen testing and all tested negative.
Bench coach James Rowson will manage the club during Mattingly's absence.
The Marlins were one of the teams deeply affected by the COVID-19 pandemic last season. An outbreak during the first week of the 60-game schedule caused 19 positive cases, with players and coaches being quarantined for six days. The outbreak resulted in nine days without games.
Despite the interruption of games last year, Mattingly helped guide the Marlins to their first postseason appearance since 2003. Mattingly was voted National League Manager of the Year.