Last week, the Uruguayans came away with a comprehensive 4-0 victory, putting them in a strong position to make the quarter-finals for the first time since 2011.
Match preview
After their defeat last Wednesday, the hopes of a first trip to the last eight of the Libertadores are in serious jeopardy for the Bolivians.
From the outset, Ismael Rescalvo's men looked out of sorts and under duress, down by three goals at half-time while rarely generating much in the attack.
The Bolivians failed to register a single effort on target throughout the 90 minutes while losing for a second successive time in this tournament by a 4-0 score.
Things are not looking promising for them, but there is a glimmer of hope given that this match takes place at home, where they had a 100% record in the group stage, failing to concede a single goal.
In addition to that they claimed a 4-0 triumph at home in the opening phase versus Huachipato, while they are unbeaten in seven consecutive competitive games played at Estadio Ernesto Siles.
Not since the 2014 Copa Libertadores have they won a round of 16 fixture, defeating Defensor 2-0, but losing the second leg by that same score and failing to advance on penalties.
An appearance in the quarter-finals appears to be virtually sealed for Penarol, who were lethal in front of goal in the opening leg.
Diego Aguirre's men have won four successive matches at the Libertadores, posting three clean sheets over that stretch.
Manyas have not conceded four goals in 90 minutes since suffering a 4-1 defeat away to Defensa y Justicia at the Copa Sudamericana last year.
Meanwhile, they are unbeaten in their last five round of 16 matches in this competition and have not been beaten at this stage since losing 3-1 to Palmeiras in 2000 before being eliminated on penalties.
This team lost two of their three away fixtures in the group stage of the tournament this year by a single goal but won the last one, 1-0 over Caracas.
Decano have lost their last two away matches against The Strongest in this competition, failing to score on either of those occasions.
The Strongest Copa Libertadores form:
L
D
W
W
L
L
The Strongest form (all competitions):
Penarol Copa Libertadores form:
W
L
W
W
W
W
Penarol form (all competitions):
W
W
W
D
W
D
Team News
From their matchday six defeat versus Gremio (4-0) to the opening leg of this tie, The Strongest added four newcomers to their starting 11, including Jeyson Chura, Abdiel Ayarza, Victor Cuellar and Jaime Arrascaita.
Goalkeeper Guillermo Viscarra has faced 10 shots on target in each of his previous two Libertadores games between the sticks and conceded four times on both occasions.
A torn muscle sustained earlier this month has left the status of Ignacio Sosa in question for Penarol heading into this encounter.
In the ninth minute, Leonardo Fernandez put his team in front before Maximiliano Silvera doubled the advantage, with Jaime Baez and Facundo Batista rounding out the scoring last week.
The Strongest possible starting lineup:
Viscarra; Caire, Aimar, Jusino, Roca; Ortega, Cuellar, Ramallo; Amoroso, Triverio, Angulo
Penarol possible starting lineup:
Aguerre; Milans, Mendez, Rodriguez, Hernandez; A. Fernandez, Darias; Cabrera, L. Fernandez, Baez; Silvera
We say: The Strongest 1-0 Penarol (Penarol advances 4-1 on aggregate)
No one expects much from the Bolivians after what happened in the opening leg, and with little pressure on their shoulders, we expect them to be a lot more compact defensively and perhaps exit the competition on a positive note.