Barcelona could suffer from the new rule that allows teams to make five substitutions in a match instead of three, their coach Quique Setien has said.
FIFA has made the temporary change to ease the physical strain on players, who are returning to a congested period of games after a lengthy break due to the coronavirus pandemic.
The law could favour the bigger clubs like Barcelona, who have deeper squads and better players ready to come off the bench.
But Setien believes Barca, who are two points clear at the top of La Liga, will also find opponents are now fresher towards the end of games.
"I think it will actually harm us," Setien said on Friday night in a video conference with the Las Palmas Football Federation.
"We know we settle a lot of matches in the final minutes. If you give the opponent the option of bringing on fresh players in that time, they won't have that weakness of tiredness.
"But it can also give you some options in certain moments. It's a bit of an unknown so we'll see how it goes."
La Liga is due to restart on June 11 after a three-month break, with the plan for the season to finish on July 19.
Teams are set to begin full training again on Monday, which would give them only 10 days working all together before competitive games resume, with many being played in the searing heat of Spanish summer.
"We thought we would have more time to work as a group but it's not to be," Setien said.
"We would have liked more time. I hope there are not many injuries and that it does less damage than people think."
Barcelona lost to Real Madrid at the Santiago Bernabeu in their penultimate match before La Liga suspended fixtures on March 11.
But Madrid's defeat by Real Betis the following weekend allowed Barca, who beat Real Sociedad, to regain top spot with 11 games left to play.