Levante will be looking to pile the misery on their neighbours, who have been gutted this summer with the exits of a number of key men.
Valencia finished in the top half last season, three points off a place in the top six, but that was considered a big disappointment.
Los Che also reached the last-16 stage of the Champions League, where they were eliminated by Atalanta 8-4 on aggregate in March.
They have since said goodbye to the likes of Ferran Torres, Rodrigo Moreno, Francis Coquelin, Ezequiel Garay and Dani Parejo without replacing them, meaning that it will be even tougher to regain a European spot for next season.
Valencia head into the new campaign with a bit of momentum on their side, having won three and drawn one of their four pre-season matches, with one of those stalemates coming against Levante.
Los Che are also unbeaten in their previous six La Liga games against Levante and could achieve their longest unbeaten run against them in the competition by avoiding defeat here.
Levante will have something to say about that, of course, and they too have gone unbeaten during this shortened pre-season campaign.
Los Granotas beat Mallorca, Cartagena and Villarreal by the same 2-1 scoreline, either side of their draw against this weekend's opponents and a 1-0 win against Castellon.
After a decent campaign last time out when finishing in a respectable 12th, Paco Lopez will perhaps be targeting a similar finish this time around.
History is not exactly on Levante's side, though, as they have only won one of their eight La Liga opening games away from home - 3-0 versus Real Betis in August 2018.
Winning at the Mestalla, fans or no fans, is also a tough task - Valencia have lost only one of their last 20 home league matches since May 2019.
Valencia pre-season form: WWDW
Levante pre-season form: WDWWW
De Frutos is in line for a debut, meanwhile, but fellow newbie Gomez may have to wait for his first competitive run-out.
Valencia possible starting lineup:
Domenech; Wass, Gabriel, Mangala, Gaya; Racic, Kondogbia; Vallejo, Lee, Guedes; Gomez
Levante possible starting lineup:
Fernandez; Miramon, Pier, Duarte, Clerc; Frutos, Campana, Radoja, Bardhi; Morales, Leon
We say: Valencia 1-1 Levante
Valencia's squad is depleted and it looks like being a tough task breaking back into the top six.
Local rivals Levante will be looking to take advantage of that, but Los Che are very tough to beat at home and we can see the points being shared in this Derby del Turia.