Inter step into Camp Nou with Lautaro Martinez, Edin Dzeko and Hakan Calhanoglu against Barcelona’s Robert Lewandowski, Raphinha and Ousmane Dembele.
It kicks off at 20.00 UK time (19.00 GMT).
The Nerazzurri won 1-0 at San Siro last week thanks to a Calhanoglu strike, although there was controversy with Barca complaining loudly in the media about a last-minute handball decision that did not warrant a VAR review.
That result put Simone Inzaghi’s men three points clear in second place, but a defeat here would put everything back in the balance.
On the other hand, a victory here and Bayern Munich avoiding defeat with Viktoria Plzen would qualify Inter for the Round of 16 already.
Marcelo Brozovic, Romelu Lukaku and Joaquin Correa are injured, so Dzeko and Lautaro Martinez are the only available senior strikers upfront.
Calhanoglu and Henrikh Mkhitaryan again form the midfield, which worked so well in the first meeting, while Denzel Dumfries is preferred to Matteo Darmian.
Barcelona are missing Memphis Depay, Jules Kounde, Andreas Christensen, Ronald Araujo and Hector Bellerin, but Franck Kessie is available again after his injury issues.
It seems to be a 4-3-3 formation, as they had been tipped to perhaps move to three at the back.
Barcelona: Ter Stegen; Sergi Roberto, Piqué, Eric García, Alonso; Pedri, Busquets, Gavi; Dembélé, Lewandowski, Raphinha
Inter: Onana; Skriniar, De Vrij, Bastoni; Dumfries, Barella, Calhanoglu, Mkhitaryan, Dimarco; Dzeko, Lautaro Martinez