The Citizens are featuring in the knockout stages of Europe's elite competition for a tenth straight year but are yet to get their hands on the trophy.
The two sides met in the Champions League group stage last season, with City stretching their 16-game unbeaten run against German opposition with a thrilling 6-3 win at the Etihad.
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But Leipzig pulled off a stunning 2-1 victory in the reverse fixture at home and will relish the opportunity to cause another upset.
Champions League round of 16 clash to kick off at 8pm.
RB Leipzig XI: Blaswich, Klostermann, Orban, Gvardiol, Halstenberg, Laimer, Schlager, Werner, Szoboszlai, Forsberg, Silva.
Subs: Nyland, Nickisch, Simakan, Haidara, Raum, Henrichs, Kampl, Poulsen, Nkunku.
Man City XI: Ederson, Walker, Akanji, Dias, Ake, Rodrigo, Gundogan, Bernardo, Mahrez, Grealish, Haaland.
Subs: Ortega, Carson, Phillips, Alvarez, Gomez, Perrone, Foden, Charles, Palmer, Lewis, Robertson.
talkSPORT will have live commentary from Jim Proudfoot and former England defender Stuart Pearce.
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