But after dealing with a string of their own injuries and coming off an "embarrassing" loss, the Spurs did not rest against their longtime rivals.
Tony Parker scored 17 points and San Antonio never trailed in rolling to 99-85 victory Friday night over a depleted Lakers team that potentially has lost Bryant to injury for the third straight season.
Bryant tore his right rotator cuff Wednesday in New Orleans. The injury will be re-examined Monday before the Lakers decide whether the superstar guard needs potentially season-ending surgery.
"It's a big change, it's totally different," Parker said of the Lakers being without Bryant. "It's not the same team, obviously. Kobe's a great leader. They made it hard on us last time we played them. It (was) different this time but for us considering the situation and coming back late, it's a good win for us."
Bryant had 22 points and nine assists in the Lakers' 112-110 overtime victory in San Antonio on Dec. 12. Without the 19-year veteran, the Lakers never trailed by less than 10 points Friday after the 4:22 mark of the opening quarter.
Kawhi Leonard had 15 points and 14 rebounds, Manu Ginobili scored 15 points and Tim Duncan added 14 points for San Antonio, which has won nine of its last 12.
The Lakers failed to hit the rim on their first two shots and shot 29 percent from the field in the opening quarter while searching for a consistent scorer without Bryant.
Nick Young scored 17 points to lead the Lakers, who lost their seventh straight. Rookie point guard and San Antonio native Jordan Clarkson had 11 points and four assists in his first career start.
One of the few bright spots was Clarkson, who had six of the Lakers' first eight points and finished 5-for-9 shooting from the field.
"I did a better job of controlling (the pace) today," Clarkson said. "Now I've just got to work on getting guys in their spots and just getting what we want in the half-court offense."
He could look to the Spurs for the blueprint on how to do so.
San Antonio used balanced scoring to cruise after jumping out to a 17-point lead in the first quarter against a Lakers team that was already minus Steve Nash and rookie Julius Randle before losing Bryant.
The Spurs led by as many as 23 points and outrebounded the Lakers 52-40.
San Antonio shot 6 for 23 in the third quarter, but still maintained a double-digit lead.
Wesley Johnson's 3-pointer pulled the Lakers within 76-66 with 10 minutes remaining in the game.
"They're NBA players," Leonard said of the rally. "The Lakers are always competitive, that's the organization. If you're not winning games, you're going to want to come out and try to win a game, you're not just going to quit. Just give them credit for fighting the whole 48 minutes."
San Antonio responded with a 7-0 run in the ensuing minute, including a 3-pointer by Patty Mills after he stripped Ronnie Price of the inbounds pass.
Coming off a humbling 104-81 loss to the Chicago Bulls on Thursday night, the Spurs were not about to let this one get away.
"It's easier to focus, to be ready when you were embarrassed," Ginobili said. "We played a terrible game yesterday, so we were willing to be back on the court and sort of redeem ourselves."
Lakers: The Lakers have missed 323 total games this season due to injury, which is almost 50 more than Denver, the second-highest team. ... G Jeremy Lin left the locker room immediately following the game after not playing for the first time in three years while active. Lin did not play due to a coach's decision as Scott used Clarkson and Ronnie Price at point guard. ... C Tarik Black missed the game after spraining his right ankle Wednesday against New Orleans. Black had six points and two rebounds in 20 minutes in the 96-80 loss to the Pelicans.
Spurs: San Antonio coach Gregg Popovich is five wins shy of 1,000 career victories. He is 995-460 in 19 seasons with the Spurs. ... G Marco Belinelli (strained left groin) missed his eighth straight game and 14th overall. ... G Danny Green is the only guard among five players in the league that are averaging at least one steal and one block per game this season.
Popovich has a reply for all the teams that are sending him literature in support of their players being selected as reserves for the All-Star game: Save the postage. "We got some interesting things in the mail from people who were politicking for their guys," Popovich said a bit tongue in cheek. "Just so that everybody who sent me something, I just want them to know it immediately went in the trash can. Such pandering is embarrassing."
Lakers: Host Houston on Sunday.
Spurs: Host Milwaukee on Sunday.