The Nets (8-15) had won three in a row for the first time this season before a 103-99 loss in Detroit on Friday. They rallied from a 21-point third-quarter deficit after being outscored 38-20 in the second, but couldn't finish the comeback without Lopez, who was sidelined with a sprained left ankle.
Lopez, listed as questionable for Monday's contest, already missed seven games in November with a sore ankle. He re-aggravated the injury when he landed awkwardly in Thursday's win over the Los Angeles Clippers.
The sixth-year center is averaging a career-high 20.5 points, but his absence was also felt on defense. Andre Drummond and Greg Monroe combined for 44 points and 24 rebounds against Brooklyn, which allowed 21 second-chance points, two shy of a season high.
The 60 points in the paint were also the most allowed this season by the Nets. Brooklyn is giving up an average of 44.0 points in the paint in eight games without Lopez, who leads the team with 1.9 blocked shots per game. The Nets have allowed an average of 36.3 in 15 games with him in the lineup.
"They are great offensive rebounders and they just pounded us out there," said Andray Blatche, who had 20 points and 12 rebounds off the bench. "The guards are driving to the basket and the bigs are just all over the boards. We definitely missed Brook, because at least he's a big body out there."
Lopez was 13 of 22 for 29 points with 11 rebounds and three blocks in Brooklyn's last meeting with Philadelphia, a 104-83 home win April 9.
Reggie Evans replaced Lopez in the starting lineup Friday but had three turnovers in less than 11 minutes of action.
"It doesn't matter who plays for us or who we're playing, we have to protect the paint and we didn't do that tonight," coach Jason Kidd said. "There's some improvement -- we kept fighting down the stretch even when we got behind -- but we can't get that far behind."
The lack of a paint presence could be a problem against Philadelphia, which ranks among the league leaders with 49.9 points in the paint per game.
However, the 76ers (7-18) have lost six in a row and own the NBA's worst record away from home at 1-10 -- only winning their first road game on Nov. 1 at Washington.
They surrendered the league's highest point total this season in a 139-105 home loss to Portland on Saturday. The Trail Blazers set a franchise record with 21 3-pointers.
"This is one of those games where they were making all their shots and all we can do sometimes is throw our hands up," Thaddeus Young said. "It's like, `What else is there to do?"
Philadelphia hasn't won since Michael Carter-Williams last played Dec. 3. The 76ers are 1-9 without the rookie point guard, who remains sidelined due to a skin infection on his right knee.
The Nets had dropped six in a row at home in the series prior to winning both meetings in Brooklyn last season.