Meszaros appeared to sustain an injury to his left shoulder on the final shift of the second period of Thursday's game when he collided with the New York Rangers' Ryan Callahan.
Meszaros had spent the lockout recovering from surgery in August to repair a torn Achilles tendon, and was questionable for the opening-night lineup.
In four games, Meszaros was a minus-1 with five shots on goal.
The Flyers likely will veteran defenseman Andreas Lilja, 37, from their American Hockey League team, the Adriondack Phantoms, to replace him. Lilja had six points in 46 games with the Flyers last season, but was waived in training camp and re-assigned to the AHL. In four AHL games he had two assists and a minus-2 rating.
Meszaros is the latest name added to Philadelphia's growing injury list. Danny Briere has not played this season due to a wrist injury sustained playing in Germany during the lockout, Zac Rinaldo is out due to a skate cut to his leg just above the knee, and Scott Hartnell is out 4-8 weeks after breaking the first metatarsal in his left foot when he was hit by a shot during Tuesday's game at the New Jersey Devils.
The team also announced Mike Knuble had joined them for the trip to Florida. The Flyers likely will officially announce his signing later Friday.