After only leading by two points at halftime, Barcelona outscored the Mavericks 32-16 in the third quarter to open up an 18-point gap. Center Chris Kaman led the Mavericks with 15 points. Darren Collison was next with 14, and Elton Brand had 10.
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Nowitzki was expected to play but was ruled out just before tip-off.
"Last year I dealt with (swelling in the knee)," Nowitzki said. "We did treatment twice and the swelling didn't come back. Hopefully it will respond next week and I can play through the year."
"It's unfortunate, I would have loved to play. But the preseason is not the time to force a swollen knee."
Two-time Euroleague champion Barcelona outrebounded the Mavericks 52-40, while Navarro hit five 3-pointers, two more than the entire Mavericks team.
Kaman scored eight points in an evenly matched first quarter that ended with Barcelona ahead 21-19.
Navarro assisted Nathan Jawai for a layup before hitting a 3-pointer to push Barcelona out to a 13-point advantage, forcing Mavericks coach Rick Carlisle to call his second time-out of the third period with 3:30 to play.
Mickeal then scored inside the paint and Marcelinho Huertas hit a bank shot before Jawai added two free throws to push the lead to 18 points.
"Today we played at a great level, with our heads held high and with a lot of motivation," Mickeal said.
The Mavericks used a full-court press to reduce the gap to six late on, but Mickeal hit back-to-back baskets to seal the win.
"Barca is a great team. I admire the way they pass, move the ball, cut and make screens. They had the advantage the whole game," Carlisle said. "Barca is an NBA team."
The Mavericks beat Alba Berlin 89-84 on Saturday in their first preseason match.
The team now return home to face Houston on Oct. 15 in Dallas and open the regular season at the Los Angeles Lakers on Oct. 30.