River Plate and Universidad Chile will try to overturn deficits in the second leg of their round of 16 Copa Sudamericana fixtures this week.
Argentinian giants River will host LDU Loja of Ecuador on Thursday, hoping to recover from a 2-1 defeat in the first leg.
Pedro Larrea and Jonny Uchuari scored the goals that gave LDU their win and they will enter the match in impressive form, having notched four wins in the last month.
On the other hand, River Plate are struggling, sitting in the bottom half of their domestic top flight after a patchy run.
This week's other second leg will see Lanus of Argentina battle with Universidad Chile.
Lanus cruised to a 4-0 home win in the first leg as Lucas Melano scored a double against a side who finished with nine men.
The Chilean outfit have not been in great form either, and Lanus will be expected to proceed comfortably.
The first leg of another five ties will also take place this week, with the headline fixture seeing 2012 winners Sao Paulo of Brazil face Chile's Universidad Catolica.
The two sides met in the semi-finals last season, with Sao Paulo progressing on away goals after they were locked at 1-1 over two legs.
The Brazilian outfit will host the first leg on Thursday and will be confident after a good run.
Sao Paulo were struggling earlier in the Brazilian Serie A season but appear to have found form at the right time.
Other first leg fixtures on Wednesday will see Brazilian clubs Coritiba and Ponte Preta host Itagui and Deportivo Pasto of Colombia respectively.
Libertad of Paraguay will welcome the visit of Brazil's Sport Recife on Thursday and Colombia's Atletico Nacional take on another Brazilian team, Bahia, on Friday.