O’Neal sat out his first game of the season on Sunday with a strained right calf. After several days of rest, the 7-foot All-Star should be back in the lineup against the Wizards.
Kobe Bryant scored 28 points, while Karl Malone had 20 points and 10 rebounds before sitting out the fourth quarter as the Lakers avenged a loss at Memphis earlier this month by routing the Grizzlies 121-89 on Sunday.
Los Angeles shot a season-high 59.2 percent even without the presence of O’Neal in the paint.
The win was the sixth in seven games for the Lakers since they committed a season-high 23 turnovers in a 105-95 loss at Memphis on Nov. 10.
The victory also extended the Lakers’ regular-season home winning streak to 22, including seven this season.
The Wizards have lost six of nine, but come to Los Angeles on a high note after beating the Portland Trail Blazers 81-80 on Tuesday.
Larry Hughes hit a driving layup with 10.3 seconds left to give the Wizards their third victory in eight road games.
Hughes finished with 22 points to lead Washington, which was without top scorer Gilbert Arenas.
Arenas was placed on the injured list earlier Tuesday because of a severe abdominal sprain. He was hurt Sunday in a loss at Seattle.
Arenas, who leads the Wizards with averages of 20.8 points and 5.5 assists a game, will miss at least five games. Washington is already missing Jerry Stackhouse, who has yet to play this season because of a knee injury.
“A lot of guys have had to step up and shoulder the load,” Wizards guard Chris Whitney said. “Larry Hughes did a good job. He’s been carrying the load all year.”