Ryan Anderson had 14 points, Xavier Henry scored 11 and Anthony Davis 10 for the Hornets, who are still last in the Western Conference at 12-26 - including matching 6-13 records at home and on the road.
Jrue Holiday led the Sixers with 29 points and 11 assists. Nick Young and Evan Turner added 14 points each while Thaddeus Young scored 12.
The Sixers have been inconsistent all season and this game was further proof following a resounding 107-100 victory Saturday over Houston. Philadelphia still hasn't won consecutive games since a three-game streak from Nov. 25-30.
The Sixers began a stretch of 12 of 13 at home with the victory over the Rockets, and appeared to have a good chance to string together a winning streak - especially with sub-.500 teams New Orleans and Toronto (Friday) coming to town.
Plus, Philadelphia received a dose of good news Monday when All-Star center Andrew Bynum took shots during practice with the coaching staff. Bynum, who has yet to play a game for his new team this season, is currently on a six-step rehabilitation process that he hopes will get him back into the lineup around the Feb. 15 All-Star break.
Bynum has been lifting weights, and he began running on Monday while saying his knees were pain-free.
But the lift from seeing Bynum work out didn't transfer into this game against New Orleans.
The Hornets outscored Philadelphia 33-21 in the third quarter, extending a six-point halftime lead to 86-68. New Orleans pushed its lead to 20 following Henry's dunk with 11:26 remaining and the fans vehemently displayed their displeasure with a cascade of boos throughout the arena.
Sixers coach Doug Collins tried to jump-start his team by putting Nick Young in the lineup to open the fourth. Young was benched against the Rockets and sat for the first three quarters against the Hornets.
But Young sparked the Sixers with 14 points in the fourth and they got within eight on a 3-pointer by Dorell Wright with 5:25 left.
The Hornets responded and quickly pushed the lead back to 105-91 after a 3-pointer by Vasquez.
New Orleans was strong throughout the first half and took a 53-47 halftime lead thanks to 57-percent shooting (24 for 42).
NOTES: The Hornets shot 16 of 21 (76.2 percent) in the first quarter. . The Sixers knocked down six 3-pointers in the first, a team high for any quarter this season. . Holiday recorded his 10th double-double of the season.