The Lakers (5-13) have yet to lose a game this season to the Eastern Conference (4-0). They will face their toughest test to date Wednesday night, visiting the Washington Wizards (11-5) after a victory Tuesday in Detroit over the Pistons, 106-96.
The Wizards are one of the top teams in the East, sitting in second place behind the Toronto Raptors (14-4), whom the Lakers upset Sunday at Staples Center.
Washington has a balanced roster led by point guard John Wall, who is averaging 18.2 points and 9.3 assists a game.
Forward-center Nene is questionable with foot issues. Martell Webster (back) is out.
The Lakers will play without Xavier Henry (Achilles' tendon), Ryan Kelly (hamstring), Steve Nash (back) and Julius Randle (leg).
The Lakers did an excellent job defending against Brandon Jennings on Tuesday, but Wall is a tougher cover.
Jeremy Lin will be charged with defending against the Wizards' point guard, who is shooting 43.3% from the field and 33.3% from behind the arc.
Wall is less of a threat from distance, instead using his speed and athleticism to attack and create.
Lin is averaging 12.4 points with 5.1 assists while shooting 47.2% from the field and 37.5% from three-point range.
Both guards can be turnover prone, Wall at 3.6 a night and Lin at 2.6.
The Wizards have a number of offensive threats, including center Marcin Gortat (13.4 points a game), Bradley Beal (13.0), Paul Pierce (12.5), Nene (10.6) and Rasual Butler (9.7).
Pierce is a longtime rival of the Lakers dating to his days with the Boston Celtics.
If the game is close, the 37-year-old Pierce can still hit a big shot.
The Lakers will need to bring a complete defensive effort, with Kobe Bryant sticking to Beal, Wesley Johnson to Pierce and Lin to Wall.
Jordan Hill, Carlos Boozer, Robert Sacre and Ed Davis will need to deal with Gortat, Nene (if he plays), Kris Humphries and Drew Gooden.
Hill has become one of the Lakers' most important players this season, averaging 14 points and 9.7 rebounds a game.
The Lakers are slightly better than their record shows, but not good enough to get the Wizards on the right half on the second night of a back-to-back.