Manager Brian Snitker said the veteran told him of his decision Sunday.
"None of us knew what this was gonna be," Snitker told O'Brien. "Until we all experience it and live it, you don't know how this is going to be."
Markakis, 36, was in camp with the team before electing to sit out the season. The father of three said talking to teammate Freddie Freeman, who recently tested positive for COVID-19, helped guide his decision.
"That opened my eyes," Markakis said, according to Gabe Burns of the Atlanta Journal-Constitution. "He didn't sound good."
Markakis joins Braves teammate Felix Hernandez, the Los Angeles Dodgers' David Price, the Washington Nationals' Ryan Zimmerman, Joe Ross, and Welington Castillo, the Colorado Rockies' Ian Desmond, the Arizona Diamondbacks' Mike Leake, and free agent Tyson Ross as players who have opted out of the shortened campaign.