James and Wade were drafted alongside each other in 2003 and have remained close ever since.
Wade was picked by the Heat, where he spent 13 years, and he was joined by James in 2010.
The pair formed a formidable partnership as they won back-to-back NBA Championships in 2012 and 2013.
But now Wade, who returned to the Heat this summer after spells with Chicago Bulls and Cleveland Cavaliers, will take to the court for one final time with James.
And the Lakers star is looking forward to the reunion – although he is desperate to help strengthen his side’s play-off chances with victory.
“It’s bitter, and it’s sweet,” said James.
“It’s sweet and sour. The sweet part about it is I’ve always loved being on the same floor with my brother.
“We struck up a relationship together at the combine in 2003, and it started from there.
“And the sour part about it is that this is our last time sharing the same court.”
James also explained why he feels emotionally connected to Wade.
“Sometimes it’s just chemistry,” James said.
“Sometimes you can’t even explain it. And I bonded with Carmelo (Anthony) when I was in the 10th grade.
“I bonded with CP3 (Chris Paul) when I was in the 12th, and I bonded with D-Wade when we were both coming into the combine.
“Some things you just can’t explain, and that’s why we have our brotherhood.”
And Wade returned the compliment when he was quizzed on the match-up.
“You’re always excited to play the Lakers, and obviously, LeBron is there and (it’s) our last time matching up, so it’s definitely going to be a little bit extra special than any normal game,” Wade said.
“I’m not going to sit here and tell you, ‘Oh, it’s another one of 82’. No, it’s not. Not for me. It’s a game where I get to play against not only one of my best friends but one of the game’s greatest players for the last time.
“I want to win as a team, but I want to savour the opportunities.”