The home side come into this game off the back of a 1-0 victory away to Bolivian side The Strongest on matchday one. An early strike by Sebastian Villa was enough to give the Argentine champions all three points.
Santos were on the wrong end of a 2-0 defeat to Ecuadorian side SC Barcelona on home soil. A second-half strike by Carlos Garces and an own goal by Para gave the visitors the victory.
Santos will be looking to get their continental campaign back on track with a win in Argentina, while Boca Juniors will be looking to consolidate their winning start.
Boca Juniors vs Santos Head-to-Head
This will be the seventh time the two sides are meeting on the continental stage and they each have fond memories of previous meetings.
The two sides clashed in the final of the 2003 Copa Libertadores, where the Argentines picked up a 5-1 aggregate victory to win their fifth Libertadores title. They followed up a 2-0 first-leg win in Argentina with a 3-1 victory in Brazil.
They also met in the semifinal stage of the competition last season when Santos secured a 3-0 aggregate victory to progress to the final.
Their earlier clash had come in the 1963 final. Pele inspired the Black and Whites to a 5-3 aggregate victory.
Boca Juniors form guide (all competitions): W-W-W-L-W
Santos form guide (all competitions): L-L-W-L-D
Boca Juniors vs Santos Team News
The hosts have three players ruled out through injury. Marcos Rojo (hamstring), Edouardo Salvio (ACL) and Diego Gonzalez (ankle) are all unavailable for selection.
Furthermore, Jorman Campuzano and Carlos Zambrano are both in self-isolation after testing positive for COVID-19.
Injuries: Edouardo Salvio, Marcos Rojo, Diego Gonzalez
COVID-19: Jorman Campuzano, Carlos Zambrano
Five players have been ruled out for the visitors ahead of the trip to Buenos Aires. Sandry, Jobson, Carlos Sanchez and Rafael Longuine have all been sidelined by ACL injuries, while Raniel has been ruled out with an Achilles tendon problem.
There are no suspension worries for head coach Ariel Holan.
Injuries: Raniel, Sandry, Rafael Longuine, Carlos Sanchez, Jobson
Boca Juniors vs Santos Predicted XI
Boca Juniors Predicted XI (4-4-2): Agustin Rossi (GK); Emmanuel Mas, Carlos Izquierdoz, Lisandro Lopes, Julio Buffarini; Agustin Obando, Agustin Almendra, Alan Varela, Cristian Medina; Sebastian Villa Cano, Franco Soldano
Santos Predicted XI (4-2-3-1): Joao Paulo (GK); Rocha Andrade, Luan Peres, Kaiky Melo, Madson; Alison Ferreira, Para; Soteldo Martinez, Gabriel Pirani, Marinho Costa; Marcos Leonardo
Boca Juniors vs Santos Prediction
Boca Juniors have more proven players within their ranks and will be looking to enact revenge for last season's loss.
They have also been in better form domestically and we are predicting a comfortable victory for the hosts.
Prediction: Boca Juniors 2-0 Santos