La Banda Roja beat Internacional 2-0 in their Group B opener, while Olimpia lost 3-2 against Deportivo Tachira and need to respond here.
Match preview
Fernando Saucedo and Carmelo Algaranaz were on target in the second half for Always Ready in their win against Internacional, seeing them get off to the perfect start.
The Bolivian champions are appearing in the Copa Libertadores for just a second time, with their only previous involvement ending in the first round 53 years ago.
Omar Asad's men followed up that victory over Internacional with a 0-0 draw at Oriente Petolero at the weekend - a result that leaves them eighth in their domestic league.
While Always Ready's league form has been mixed in the early stages of the season - two draws, two wins and a loss - they have made a good start to their continental campaign.
The opposite is true for Olimpia in many ways, as a 2-1 win against Club Guarani last time out saw them move level on points with Paraguayan Primera Division leaders Libertad.
That came on the back of a topsy-turvy affair with Tachira last week, with Lucas Trejo ultimately settling that match with a winning goal 10 minutes from time.
Paraguayan champions Olimpia have far more experience of playing in the Copa Libertadores, and they have won the competition on three previous occasions, most recently in 2002.
Sergio Orteman will know the importance of his side hitting back from the loss to Tachira - their only defeat in six matches - with all three points on Wednesday.
This will be the first ever competitive encounter between the two clubs, and the result could go a long way to determining which side advances to the last 16.
Olimpia Copa Libertadores form:
Olimpia form (all competitions):
Always Ready Copa Libertadores form:
Always Ready form (all competitions):
Team News
Carmelo Algaranaz scored as a second-half substitute against Internacional to seal the win and may be considered for a starting spot on Wednesday.
Marc Enoumba, Samuel Galindo and John Mosquera are the other Always Ready players pushing for inclusion from the opening Copa Libertadores outing.
As for the home team, they will be forced into at least one change as Alejandro Silva was sent off for two bookable offences against Tachira.
Juan Rodrigo Rojas is the most likely contender to come into the side down the right, while Edwar Lopez is another pushing for a recall.
Former River Plate attacker Roman Sosa was on target against Tachira and now has three goals in 11 appearances in all competitions this season.
Olimpia possible starting lineup:
Aguilar; Otalvaro, Caceres, Alcaraz, Torres; Rojas, Ortiz, Quintana, Sosa; Recalde, Santa Cruz
Always Ready possible starting lineup:
Lampe; Cummings, Cabrera, Flores; Ramallo, Machado, Arce, Saucedo, Vander; Ovejero, Sanguinetti
We say: Olimpia 1-1 Always Ready
Always Ready picked up an impressive win against Internacional in their Group B opener and are unbeaten in five games in all competitions, keeping a clean sheet in three of those.
Olimpia need to respond to their loss against Tachira and, having netted in their last 11 games, we can see them picking up a point in a score draw.