James is expected to miss two weeks after tests revealed injuries to the superstar's left knee and lower back.
The Cavaliers announced in a release Thursday that multiple examinations, including an MRI, showed that James has knee and back strains. The tests were performed Wednesday before the Cavs lost their third straight game, a 96-80 loss to the Milwaukee Bucks.
"First and foremost, we want to make sure LeBron is well and completely recovered," Cavs coach David Blatt told the Northeast Ohio Media Group on Thursday. "The season is long and our main objective is that he will be well and strong for the rest of the season. But we have to fight it out and work every day to build others until he gets back after the time he needs."
James, who has missed Cleveland's past two games, will undergo several forms of treatment, including anti-inflammatories, the team said. The four-time MVP has never missed more than five straight games in his professional career; if the two-week timetable holds up, his absence could reach 10 games or more.
The Cavs play in Charlotte on Friday, host Dallas on Sunday, visit Philadelphia on Monday, are back home to meet Houston on Wednesday -- then head out for a five-game road trip against Western Conference clubs. Cleveland is 0-3 this season when James does not play.
James aggravated his nagging knee injury on Christmas Day in Miami while jumping over a row of courtside seats. He acknowledged that the knee has been "hurting pretty much all year" on Wednesday, one day after his 30th birthday.
"I've been playing with it, and it goes away and comes back," he said. "So, the one in Miami kind of reaggravated it when I came out of the game in the third quarter."
Even though James was not required to speak to the media Wednesday because he was out of the lineup, he made himself available to answer a slew of questions in the locker room before the Bucks game about his health and the controversy surrounding his commitment to staying in Cleveland beyond this summer.
"I'm here to build something great in the present and in the future, and that's the reason I'm back," James said. "I got no other reason to have to continue to talk about things that's so outlandish. I'm here. This is where I'll be, and this is where I'm comfortable at."
A source told the Northeast Ohio Media Group that team physician, Dr. Richard Parker made his diagnosis after James had spoken with reporters.
The Cavs were also without Kevin Love (back spasms) and Shawn Marion (sore left ankle) on Wednesday, making for another challenging night for Cleveland while playing the second leg of a back-to-back. Brandon Knight scored 26 points, and the Bucks led most of the way in the win.
"Not having Andy too requires a whole different approach and we are working on that as well," Blatt told Northeast Ohio Media Group. "Getting Kevin and (Marion) back in the short term will be important, and we will. We've just got to fight it out. There's no easy answer."
A preseason favorite to contend for the NBA title, the Cavaliers (18-14) have lost four of their past five games -- a stretch that has fueled widespread speculation about first-year coach Blatt's job security.
James said that he and the team simply must stay the course.
"Just stay even keel and knowing that there's always sunshine on the other side of the mountain, man," James said. "I don't get too high or too low, especially in the NBA season. It's too long, it's too many emotions, it's too many things, it's too many storylines that if you let yourself get involved in it too much that it can bother you mentally, and I've been able to just stay away from it."
ESPN.com's Dave McMenamin and The Associated Press contributed to this report.