Nkunku left Leipzig in 2023 for Chelsea before joining Milan last summer, where he scored just eight times in 35 appearances for the Italians.
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He scored 70 goals in a previous four-year spell with Leipzig, which included two German Cup successes and being named Germany's player of the year in 2022.
The 28-year-old made the last of his 18 Les Bleus appearances in November.
"When I heard of the opportunity to join RB Leipzig, I immediately wanted to say yes," Nkunku said in a club statement.
"I'm very happy to be back here.
"My connection to RB Leipzig is very special. Even after leaving the club, I continued to keep a close eye on what was happening here.
"I'm now ready to add a new chapter to my time here at RBL."