The Sixers let a 10-point lead slip away in the fourth quarter and struggled defensively as they allowed a career-best 53 points from T.J. Warren.
Philadelphia (39-27) will enter this game as the No. 6 seed in the Eastern Conference, one full game behind the Pacers.
In the six-point loss, the Sixers also committed 21 turnovers.
"It was some humble pie, to be honest, to really affirm to us that any team at any time can have a good game and can beat you," said guard Tobias Harris, who scored 30 points.
Joel Embiid's performance was a bright spot after missing the final two scrimmages with a strained right calf. Embiid compiled 41 points, 21 rebounds, four assists and three blocked shots, but ultimately the Sixers came up short.
Embiid also was seen arguing strongly with teammate Shake Milton at the end of the first quarter.
"It's basketball. Everybody makes mistakes," Embiid said. "It happens. We've got to come in and get better. But it's nothing. It happens everywhere. We discussed about what's going on and moved on. We find a solution. It's nothing."
Milton's first game at point guard did not go well with Ben Simmons moved to power forward. Milton went scoreless and picked up five fouls in limited playing time.
"I thought he got sped up in his mind," Sixers head coach Brett Brown said of Milton. "He got scored on initially pretty quickly. We had a discussion about pick-and-roll defense with him and Joel, about that direction the screen was coming. And I thought he chased for the most part all game."
The Spurs (29-36) enter this matchup against the Sixers with some positive momentum.
After a win over the Sacramento Kings on Friday in their first game in the bubble, the Spurs followed with a 108-106 victory Sunday over the Memphis Grizzlies. As a result, the Spurs moved from 12th place in the Western Conference to ninth and just two games out of the eighth spot.
DeMar DeRozan knocked down two free throws with one second left to seal the win Sunday and push the Spurs within two games of the Grizzlies.
The Spurs have advanced to the playoffs 22 straight seasons.
"I don't really think it matters where we stand after (two wins)," center Jakob Poeltl said. "It's going to matter where we stand after the eight games. Obviously against the teams that are in the fight with us, like Sacramento (and Memphis), it's going to mean a little more. These are going to be sort of must-win games."
As usual, the Spurs will be ready to play.
"We are all just happy to have basketball back," Murray said. "We love the game and we want to go out and continue to keep this thing going. We are just happy to have our love back."
--Field Level Media