Leon and Club America will meet in a rematch of last month's Apertura final in Liga MX's round three, while leaders Queretaro are on the road.
Despite travelling to the Estadio Azteca for the match, Leon will be buoyed by the memories of lifting their sixth championship at the stadium on December 16.
The title holders have started the season with a win and draw and possess the competition's most prolific striker Carlos Pena, who has struck three times in their two matches.
America's 3-0 win over Tigres on the opening day was offset by a single goal loss at Tijuana and the Mexican giants will be keen to get back to winning ways on Saturday.
Queretaro will aim to remain the division's only team with a 100 per cent winning record as they travel to Monterrey.
Two single goal victories over Morelia and Pumas UNAM have earned Queretaro a strong start to the season as they attempt to improve on their seventh-placed position last campaign.
Monterrey have started their season with two draws and will be looking for their first win to rise up the standings.
Tijuana, along with Queretaro, are the only Liga MX teams to have not conceded a goal and they will attempt to continue that record with a trip to Pachuca, who are one of two sides yet to find the back of the net.
The other team looking to get on the scoresheet for the first time this season is Tigres UANL - who face a tricky trip to Morelia.
In other matches, Santos Laguna will host Puebla, Veracruz welcomes Guadalajara and Chiapas takes on Cruz Azul.
Atlas and Atlante lock horns with both looking for their first win and Toluca will be on the road against Pumas UNAM.