Los Che advanced to the group stages of the Champions League as a result of their aggregate victory over Monaco, despite their 2-1 defeat at the Stade Louis II.
Santo's side will now turn their attention back to the league after they got off the mark on the opening day with a 0-0 draw against Rayo Vallecano.
Valencia had several chances to win the match, but they were thwarted in their attempts to take all three points on the opening day as their forwards failed to fire in front of goal.
Los Che's home form last season was crucial to their fourth-place finish to guide them into the Champions League. They lost just once last season at the Mestalla and won 15 of their 19 matches, with only champions Barcelona and Real Madrid boasting a better record.
Valencia's struggles to find the net in their opener were surprising given that they notched 70 goals in the league last season, 42 of which came at home. Daniel Parejo led the way with 12 strikes in the league, but Alvaro Negredo will be determined to find his form this season after making his loan move permanent.
Santo will be targeting his side's first win of the campaign to kickstart their challenge to remain in touch with Barcelona and Real to better their finish from last season.
Recent league form: D
Recent form (all competitions): WDL
Deportivo La Coruna
Deportivo opened their 2015-16 season with a 0-0 draw in their clash against Real Sociedad to get them off the mark for the campaign.
Victor Sanchez's men got off to a solid start as they fended off a strong challenge from David Moyes's side to earn a valuable point in the first game of the season at Estadio Riazor.
Deportivo survived relegation to the Segunda Division by the skin of their teeth as Elche were condemned to life in the second tier due to their financial debt, much to the relief of Sanchez as well as Eibar and Granada at the foot of the table.
Brancoazuis had a poor record on the road last season as they won just two of their 19 games away from the Estadio Riazor, losing nine of their matches.
Goals were the main problem for Deportivo as they scored just 13 times away from home - only relegated Cordoba scored fewer on their travels. Lucas Perez was the club's top scorer last season with six goals and Sanchez will be hopeful that someone his side takes the initiative to break into double figures in the campaign.
Brancoazuis will face a tough task to improve their away record from last season when they travel to the Mestalla on Sunday.
Recent league form: D
Sanchez is likely to stick with the same lineup that drew against Sociedad. Alberto Lopo should be able to overcome a knock to play in the clash at the Mestalla.
Valencia possible starting lineup:
Ryan; Cancelo, Vezo, Mustafi, Gaya; Paul, Fuego, Parejo; Mina, Alcacer, Piatti
Deportivo possible starting lineup:
Lux; Laure, Sidnei, Lopo, Navarro; Borges, Mosquera; Juanfran, Fajr, Cani; Perez
Head To Head
Over the course of history, the teams are tied at 18 wins apiece out of their 46 contests, while 10 of the matches have ended in draws.
We say: Valencia 3-0 Deportivo
Valencia lost during the week although they still edged past Monaco into the group stage of the Champions League.
Santo will be eyeing a victory for his team to get their first win of the league campaign and Los Che will able to dominate Deportivo due to their superior quality in the final third of the pitch.